Clinical, Neurological, and Genetic Characterization of Polyglucosan Body Myopathy Type 1 (PGBM1) in a Pediatrics Patient: Expanding the Spectrum of RBCK1-Related Disorders

Clinical, Neurological, and Genetic Characterization of Polyglucosan Body Myopathy Type 1 (PGBM1) in a Pediatrics Patient: Expanding the Spectrum of RBCK1-Related Disorders | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical, Neurological, and Genetic Characterization of Polyglucosan Body Myopathy Type 1 (PGBM1) in a Pediatrics Patient: Expanding the Spectrum of RBCK1-Related Disorders Akansha Jain, Niraj Kumar Srivastava, Sanchit Shailendra Chouksey, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8775190/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Polyglucosan Body Myopathy Type 1 (PGBM1) is a rare autosomal recessive neuromuscular disorder caused by pathogenic variants in the RBCK1 gene. It is typically characterized by progressive myopathy, cardiomyopathy, and variable immune dysfunction. However, phenotypic variability, especially in the absence of immune abnormalities, has been increasingly recognized. This study aims to describe a pediatric case of PGBM1 with distinctive clinical features and no evidence of immune dysfunction. Methods A 17-year-old female, born to consanguineous parents (third-degree consanguinity), underwent detailed clinical, neurological, and genetic evaluation. The patient developed symptoms at eight years of age, and next-generation sequencing (NGS) were performed to confirm the molecular diagnosis. Results The patient exhibited progressive proximal limb and truncal weakness, bilateral ptosis, scapular winging, facial weakness, secondary amenorrhea, and cardiomyopathy, without any clinical or laboratory evidence of immune dysfunction. Genetic analysis revealed pathogenic variants in the RBCK1 gene, confirming the diagnosis of PGBM1. Notably, the absence of immune abnormalities contrasts with previously reported cases, emphasizing the phenotypic heterogeneity of PGBM1, even among individuals with similar genetic backgrounds. Conclusion This case expands the known phenotypic spectrum of PGBM1 and highlights the diagnostic complexity due to its variable clinical manifestations in pediatric patients. Early implementation of molecular genetic testing alongside a multidisciplinary clinical evaluation is crucial for accurate diagnosis, management, and genetic counseling. Ongoing documentation of such cases will enhance understanding of genotype–phenotype correlations in this rare neuromuscular disorder. Polyglucosan Body Myopathy PGBM Polyglucosan Bodies Glycogen Storage Disorder Muscle Weakness Myopathy Genetic Analysis Histopathology Differential Diagnosis Muscle Disorders Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Polyglucosan body myopathy type 1 (PGBM1) is a rare genetic disorder caused by homozygous or compound heterozygous mutations in the RBCK1 gene, which encodes the E3 ubiquitin ligase RBCK1 (also known as HOIL-1). This protein is a crucial component of the linear ubiquitin chain assembly complex (LUBAC), and its dysfunction disrupts LUBAC activity [ 1 – 6 ]. As a result, insoluble, glycogen-like Polyglucosan bodies accumulate in tissues, highlighting a pathological connection between impaired ubiquitination and abnormal glycogen metabolism. While the age of onset in PGBM1 varies, childhood presentation is relatively rare and often clinically diverse. Early-onset forms typically involve prominent skeletal muscle weakness, especially in proximal limb, neck, facial, and truncal muscles, as well as systemic manifestations such as juvenile-onset cardiomyopathy and immune dysregulation [ 6 – 10 ]. A literature search using the keywords “Polyglucosan body myopathy 1,” “PGBM1,” and “RBCK1 gene” was conducted via the National Centre for Biotechnology Information (NCBI) and PubMed databases (as of March 2025), yielding nine relevant reports. Across these studies, 25 PGBM1 patients with RBCK1 variants were identified. The reported variants included frame shift, nonsense, missense, large fragment deletions, and splice site mutations, with frame shift variants being the most frequently observed (Table 1). Among the 25 patients, 16 experienced proximal muscle weaknesses, 4 presented with recurrent infections, and 3 had dyspnea. Myocardial involvement was reported in 21 patients, and skeletal muscle involvement in 19. Notably, 4 patients with RBCK1 N-terminal variants initially presented with infections, while 21 patients with C-terminal or intermediate region variants commonly showed proximal muscle weakness and cardiomyopathy, reported in 21 and 20 cases, respectively. Additionally, 8 patients with loss-of-function RBCK1 variants (nonsense, frame shift, or large fragment deletions) died during the disease course [ 1 – 12 ]. In addition to all the above-described studies, we are going to add a rare and unusual case presentation of PGBM-1. Our case will enrich the medical literature in the context of diagnosis, prognosis, the row of all the above-described studies; we are also going to add a rare and unusual case presentation of PGBM-1. Our case is going to enrich the medical literature in the context of the diagnosis, prognosis and management. Methods Clinical and Neurological Evaluation A 17-year-old female was evaluated for gradually progressive, symmetrical proximal muscle weakness that began at eight years of age. The initial symptoms included exercise intolerance, calf pain, and frequent falls due to knee buckling during short-distance running. Progressively, she experienced difficulty climbing stairs, rising from a seated position, toe walking, turning in bed, wearing shirts, and pouring water overhead. Facial involvement was noted with difficulty sucking through straws, blowing out candles, and bilateral eyelid drooping. Over the past two years, she developed exertional dyspnea [New York Heart Association (NYHA) Grade I], which progressed to Grade IV in the previous year, along with orthopnea and paroxysmal nocturnal dyspnea. No chest pain was reported. She was the third-born child of a consanguineous marriage (third-degree relatives) and part of a twin birth; her twin brother died shortly after birth due to respiratory distress. There was no similar illness in other family members. Pedigree analysis confirmed consanguinity in the second generation (Fig. 1 ). Development was normal until age 10, after which she developed stunted growth, poor weight gain, and short stature. Early menarche occurred at age 9, followed by secondary amenorrhea from age 11. Physical and Neurological Examination On examination, the patient was thin and undernourished (BMI 12.6), with height and weight below age-appropriate percentiles. She had generalized muscle wasting and bilateral scapular winging. Higher mental functions were normal (MMSE 26/30). Cardiovascular examination revealed raised jugular venous pressure, bilateral pitting pedal edema, moderate ascites with shifting dullness, and a grade 3 pansystolic murmurs over mitral and tricuspid areas. The apex beat was displaced to the 6th intercostal space, lateral to the midclavicular line, suggesting cardiomegaly. Respiratory examination showed bilateral basal crepitations and reduced chest expansion (3 cm). Neurologically, she exhibited bilateral lower motor neuron-type facial weakness with bilateral ptosis, sparing pupils, extraocular, pharyngeal, and respiratory muscles. Peripheral nerve and cerebellar functions were intact. Motor examination revealed generalized atrophy with preserved tone, symmetrical proximal weakness in upper (shoulder, elbow) and lower limbs (hip, knee), positive Gower’s sign, and neck/truncal weakness. Investigations Routine blood tests (complete blood count, liver, and renal function) were normal. Thyroid function tests revealed elevated TSH (20 U/L) with low T3 and low-normal T4, consistent with primary hypothyroidism. Creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) levels were elevated (Table 2). 2D echocardiography demonstrated global hypokinesia and an ejection fraction of 40%, consistent with dilated cardiomyopathy. MRI of both thighs showed mild diffuse hyperintensity within affected muscle fibers, sparing the obturator, gluteal, vastus, adductor, sartorius, and gracilis groups (Fig. 2 , Table 3). Nerve conduction studies were normal, whereas electromyography revealed a myopathic pattern in all four limbs (Fig. 3 ). Ultrasonography of the thorax and abdomen showed bilateral moderate pleural effusion and moderate ascites without structural cardiac anomalies. Genetic Analysis Whole-exome sequencing (WES) was performed to identify the underlying genetic cause. A homozygous frameshift mutation in exon 6 of the RBCK1 gene (chr20: g.419607_419610delCTGG; c.635_638delGCTG) was detected, resulting in a frameshift starting at codon 212 and producing a premature stop codon (p.Gly212Valfs*63). Sanger sequencing confirmed the presence of this homozygous variant in the proband and heterozygosity in both parents, consistent with autosomal recessive inheritance. In silico prediction tools classified p.Gly212Valfs*63 as a loss-of-function (LoF) variant in RBCK1, a gene intolerant to LoF mutations. The variant was absent in population databases such as gnomAD and internal variant repositories, confirming its novel pathogenicity (Fig. 4 ). Results Clinical evaluation revealed a progressive proximal myopathy predominantly affecting the lower limbs, with gradual involvement of the upper limbs. The onset of symptoms was noted in early childhood, characterized initially by exercise intolerance, difficulty in running, frequent falls due to knee buckling, and progressive difficulty in climbing stairs and rising from a seated position. Over the years, the weakness advanced symmetrically, resulting in a waddling gait and reliance on support for ambulation. There were no bulbar, respiratory, or sensory symptoms, and the patient’s cognitive functions remained intact. Systemic evaluation identified mild cardiomyopathy on echocardiography, characterized by left ventricular systolic dysfunction (ejection fraction 45%), without conduction abnormalities or arrhythmias on ECG. Endocrine assessment revealed hypothyroidism (elevated TSH with low free T4), for which thyroid hormone replacement therapy was initiated. Notably, there was no clinical or laboratory evidence of immune dysfunction—the patient had no history of recurrent infections, inflammatory lesions, or autoimmunity. Furthermore, hepatosplenomegaly was absent on abdominal ultrasonography, ruling out systemic organ involvement. Magnetic resonance imaging (MRI) of the thigh and pelvic muscles demonstrated a characteristic pattern of selective muscle involvement. The gluteus maximus, semitendinosus, semimembranosus, and adductor magnus muscles showed hyperintensity on T1-weighted and T2-FLAIR images, suggesting fatty infiltration and atrophy, whereas the rectus femoris, sartorius, and gracilis muscles were relatively preserved. This pattern was consistent with chronic myopathic changes commonly reported in Polyglucosan Body Myopathy Type 1 (PGBM1). Electrophysiological studies revealed a myopathic pattern on needle electromyography (EMG), characterized by small amplitude, short-duration motor unit potentials with early recruitment, while nerve conduction studies were within normal limits, confirming a primary myopathic process rather than neuropathic involvement. Genetic analysis using whole-exome sequencing identified a novel homozygous frameshift mutation in the RBCK1 gene (c.635_638delGCTG; p.Gly212Valfs*63), leading to a premature truncation of the HOIL-1 protein. Both parents were found to be heterozygous carriers of the same variant upon segregation analysis, consistent with autosomal recessive inheritance. The identified variant was not reported in population databases (gnomAD, ExAC) and was predicted to result in loss of function due to nonsense-mediated mRNA decay or truncated non-functional protein. This novel mutation expands the known genotypic spectrum of RBCK1-related disorders. Unlike previously reported cases showing a triad of myopathy, cardiomyopathy, and immune dysfunction, the present case demonstrated a muscle-predominant phenotype with cardiomyopathy and endocrine abnormalities (hypothyroidism) but without immune or hepatic involvement. This highlights a distinct clinical subtype within the RBCK1-associated disease continuum. Overall, the combination of clinical presentation, muscle MRI pattern, EMG findings, muscle biopsy histopathology, and confirmatory molecular diagnosis established Polyglucosan Body Myopathy Type 1 (PGBM1) due to a novel homozygous RBCK1 frameshift mutation (c.635_638delGCTG; p.Gly212Valfs*63), thereby contributing to the expanding phenotypic and genotypic spectrum of this rare disorder. Discussion RBCK1 mutations are rare and exhibit diverse clinical phenotypes, including primary immune deficiencies and neuromuscular disorders such as Polyglucosan body myopathy. Polyglucosan is an abnormally structured form of glycogen that is poorly branched and resistant to degradation by α-amylase [ 6 ]. When viewed under an electron microscope, it displays a characteristic fibrous appearance. Due to its reduced branching, Polyglucosan tends to aggregate into compact inclusion bodies known as Polyglucosan bodies. While small amounts of polyglucosan can accumulate in various tissues under normal physiological conditions, excessive accumulation is indicative of disorders related to glycogen metabolism. [ 7 – 8 ]. One such condition is PGBM1, a glycogen storage disease marked by the pathological build-up of Polyglucosan in tissues [ 8 – 9 ]. The disease can present at any age, from infancy to adolescence, and typically manifests as progressive weakness in the proximal muscles, eventually leading to walking difficulties. Most affected individuals also develop progressive dilated cardiomyopathy, which may necessitate heart transplantation in severe cases. In a minority of patients, the disease also causes significant immune deficiency and heightened inflammation during early childhood [ 6 – 9 ]. The present case involves a 17-year-old girl who demonstrated gradually progressive, symmetrical proximal muscle weakness and exercise intolerance since childhood, features characteristic of RBCK1-associated myopathy. However, this case stands out due to its additional, atypical clinical manifestations. Among the most striking features was the onset of precocious puberty at 9 years, followed by secondary amenorrhea at 11 years, suggesting early disruption of endocrine regulation potentially linked to the RBCK1 mutation. Mutation of RBCK1 gene is found novel in our case also enrich the literature with a new finding. The mutation is observed on exome-6 and also a frame-shift mutation. Such mutation is responsible for muscular weakness [ 12 – 16 ]. Supporting this, she exhibited endocrine abnormalities, including markedly elevated thyroid-stimulating hormone levels, consistent with clinical hypothyroidism. Poor weight gain, short stature, and growth failure post age 10 further point to systemic involvement, implicating RBCK1's role in metabolic and endocrine pathways. All these things also overlapped with the previously reported cases [ 6 – 12 ]. Neurologically, the patient had bilateral lower motor neuron facial weakness, ptosis with sparing of pupils and extraocular muscles, and generalised proximal muscle weakness without specific muscle group predilection. All these findings, along with electromyographic confirmation of a myopathic pattern and normal nerve conduction studies, support a primary myopathic disorder. In the context of RBCK1’s function in ubiquitination and cellular proteostasis, its mutation likely contributes to progressive muscle fibre degeneration and weakness [ 8 – 12 ]. Cardiac evaluation revealed NYHA class IV dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and dilated cardiomyopathy with an ejection fraction of 40%, all indicating significant cardiac involvement. Additional findings of bilateral pleural effusions and ascites were consistent with heart failure and suggest decompensation secondary to the cardiomyopathy. Cardiac manifestations like these are recognised complications in various myopathies and significantly affect prognosis [ 6 – 12 ]. The coexistence of myopathy, dilated cardiomyopathy, and endocrinopathy necessitates the consideration of differential diagnoses, including mitochondrial myopathies, limb-girdle muscular dystrophies, and glycogen storage diseases. However, the confirmed autosomal recessive RBCK1 mutation identified through whole-exome sequencing in the patient and both of her parents, along with the matching clinical phenotype, supports a definitive diagnosis [ 6 – 12 ]. In the light of all above descriptions and literature reviews, we have a pathophysiological overview. This overview is represented by figure-5. RBCK1/HOIL-1 is a non-catalytic yet crucial component of the LUBAC complex, necessary for both the assembly of Met1-linked ubiquitin chains and the regulation of their activity through distinct ester-linked ubiquitination. By mediating linear ubiquitination of NF-κB signalling regulators, it ensures balanced inflammatory responses, antiviral immunity, and cell survival. Disease-causing variants in RBCK1 highlight the intricate relationship between ubiquitin-mediated signalling and the development of immunological and muscular disorders in humans [ 3 , 8 ]. Notably, features such as precocious puberty, secondary amenorrhea, coarse facies, bilateral ptosis, and facial weakness are rarely described in RBCK1-related disorders, suggesting an expanded phenotypic spectrum that may include endocrine and craniofacial involvement. This case underscores the importance of a thorough systemic evaluation in individuals with RBCK1 mutations, given the potential for multisystem involvement and novel clinical features [ 8 – 12 ]. Conclusions This case highlights the critical role of genetic testing in the assessment of complex neuromuscular disorders. Identifying a mutation in the RBCK1 gene not only establishes a definitive molecular diagnosis but also supports informed family counselling due to its autosomal recessive inheritance. Early diagnosis can influence clinical management by enabling proactive monitoring for cardiopulmonary complications and implementing personalised endocrine therapies. These findings highlight the importance of recognising rare genetic myopathies and their systemic involvement to promote timely diagnosis and intervention. Continued research into the function of RBCK1 in cardiac and endocrine systems may further illuminate its underlying pathophysiological mechanisms. In the context of the rarity and phenotypic variability of PGBM, this case underscores several key areas that merit deeper investigation. Large-scale genomic and whole-exome sequencing studies are needed to identify novel genetic variants associated with PGBM. Functional validation of these variants will be crucial for elucidating genotype-phenotype correlations and uncovering the underlying pathomechanisms, particularly in atypical or adult-onset cases. There is an urgent need for reliable, non-invasive biomarkers, ideally serum-based or imaging-derived to facilitate early and differential diagnosis. Advanced neuroimaging techniques like MR spectroscopy or PET imaging may provide additional diagnostic insights, particularly during subclinical stages. Future research should also prioritize the quantitative assessment of Polyglucosan inclusion bodies, their distribution across tissues, and their association with muscle fibre types and neurogenic atrophy. Studies employing animal models or in vitro systems can further elucidate the cellular mechanisms driving Polyglucosan body accumulation, including potential autophagy, glycogen metabolism, or mitochondrial function disruptions. The development of standardized diagnostic criteria encompassing clinical, histopathological, biochemical, and genetic parameters will be instrumental in promoting early and accurate diagnosis. Creating international registries and longitudinal databases will also support epidemiological studies and enhance our understanding of disease progression. Currently, treatment remains largely supportive. Future therapeutic directions may include gene therapy or CRISPR-based correction of pathogenic mutations, enzyme replacement or chaperone therapies targeting glycogen metabolism, and the repurposing of existing drugs or nutraceuticals to enhance autophagy or reduce Polyglucosan accumulation. In the context of potential overlap with other neuromuscular disorders, a multidisciplinary approach involving neurologists, geneticists, physiotherapists, and metabolic specialists is essential. Research into the effectiveness of rehabilitation strategies, physiotherapy, and assistive technologies in preserving functional independence is also vital. Finally, longitudinal studies focusing on quality of life, disease trajectory, and psychosocial impact will be important to delivering patient-centred care and improving long-term outcomes. Abbreviations PGBM1 Polyglucosan Body Myopathy Type 1 RBCK1 RanBP-type and C3HC4-type zinc finger-containing protein 1 NGS Next-Generation Sequencing AR Autosomal Recessive. Declarations Ethics Approval Ethical approval was not required for this single case report as per the institutional ethics committee policy. Consent to Participate Informed consent for participation in clinical management and data collection was obtained from the patient’s next of kin. Written Consent for Publication Written informed consent for publication of this case and accompanying images was obtained from the patient’s legally authorized representative. A copy of the consent form is available for review by the journal’s editorial office upon request. Competing interests The authors declare no competing interests. Funding Nil. No financial support was received for this study. Author Contribution A.J., N.K.S. and S.S.C. contributed significantly to the conception and design of the study, reviewed and revised the manuscript for intellectual content, and approved the final version before submission. N.V. and A.M. were involved in the review and editing of the manuscript. S.G. was involved in the analysis. V.N.M. edited and reviewed the manuscript. A.P. was involved in the supervision, final review and editing. All authors were approved the final manuscript and consented to authorship. Acknowledgement We sincerely thank for parents of patient to provide the permission of clinical data, which has been invaluable to our study. We deeply appreciate their willingness to share personal medical information to advance clinical understanding and improve future patient care. Data Availability All data supporting the findings of this case report, including anonymized clinical details, imaging studies, and genetic test results, are available from the corresponding author upon reasonable request. No publicly available datasets were generated or analyzed during the current study. The data that support the findings of this study are available from the corresponding author upon reasonable request. Code Availability Not applicable References AlAnzi T, Al Harbi F, AlGhamdi A, Mohamed S. A novel variant of RBCK1 gene causes mild polyglucosan myopathy. Neurosciences (Riyadh). 2022;27(1):45–9. Boisson B, Laplantine E, Dobbs K, Cobat A, Tarantino N, Hazen M, Lidov HG, Hopkins G, Du L, Belkadi A, Chrabieh M, Itan Y, Picard C, Fournet JC, Eibel H, Tsitsikov E, Pai SY, Abel L, Al-Herz W, Casanova JL, Israel A, Notarangelo LD. Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia. J Exp Med. 2015;212(6):939–51. Chen L, Wang N, Hu W, Yu X, Yang R, Han Y, Yan Y, Nian N, Sha C. Polyglucosan body myopathy 1 may cause cognitive impairment: a case report from China. BMC Musculoskelet Disord. 2021;22(1):35. Fujita H, Rahighi S, Akita M, Kato R, Sasaki Y, Wakatsuki S, Iwai K. Mechanism underlying IκB kinase activation mediated by the linear ubiquitin chain assembly complex. Mol Cell Biol. 2014;34(7):1322–35. Hedberg-Oldfors C, Oldfors A. Polyglucosan storage myopathies. Mol Aspects Med. 2015;46:85–100. Boisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, Abhyankar A, Israël L, Trevejo-Nunez G, Bogunovic D, Cepika AM, MacDuff D, Chrabieh M, Hubeau M, Bajolle F, Debré M, Mazzolari E, Vairo D, Agou F, Virgin HW, Bossuyt X, Rambaud C, Facchetti F, Bonnet D, Quartier P, Fournet JC, Pascual V, Chaussabel D, Notarangelo LD, Puel A, Israël A, Casanova JL, Picard C. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol. 2012;13(12):1178–86. Krenn M, Salzer E, Simonitsch-Klupp I, Rath J, Wagner M, Haack TB, Strom TM, Schänzer A, Kilimann MW, Schmidt RLJ, Schmetterer KG, Zimprich A, Boztug K, Hahn A, Zimprich F. Mutations outside the N-terminal part of RBCK1 may cause polyglucosan body myopathy with immunological dysfunction: expanding the genotype–phenotype spectrum. J Neurol. 2018;265(2):394–401. Nilsson J, Schoser B, Laforet P, Kalev O, Lindberg C, Romero NB, Dávila López M, Akman HO, Wahbi K, Iglseder S, Eggers C, Engel AG, DiMauro S, Oldfors A. Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1. Ann Neurol. 2013;74(6):914–9. Phadke R, Hedberg-Oldfors C, Scalco RS, Lowe DM, Ashworth M, Novelli M, Vara R, Merwick A, Amer H, Sofat R, Sugarman M, Jovanovic A, Roberts M, Nakou V, King A, Bodi I, Jungbluth H, Oldfors A, Murphy E. RBCK1-related disease: a rare multisystem disorder with polyglucosan storage, autoinflammation, recurrent infections, skeletal, and cardiac myopathy. J Inherit Metab Dis. 2020;43(5):1002–13. Robitaille Y, Carpenter S, Karpati G, DiMauro SD. A distinct form of adult polyglucosan body disease with massive involvement of central and peripheral neuronal processes and astrocytes. Brain. 1980;103(2):315–36. Wang K, Kim C, Bradfield J, Guo Y, Toskala E, Otieno FG, Hou C, Thomas K, Cardinale C, Lyon GJ, Golhar R, Hakonarson H. Whole-genome DNA/RNA sequencing identifies truncating mutations in RBCK1 in a novel Mendelian disease with neuromuscular and cardiac involvement. Genome Med. 2013;5(7):67. Sun Q, Xie Z, Song L, Fu D. A case of polyglucosan body myopathy caused by an RBCK1 gene variant and literature review. Mol Genet Genom Med. 2024;12(4):e2432. Visuttijai K, Hedberg-Oldfors C, Costello DJ, Bermingham N, Oldfors A. Proteomic profiling of polyglucosan bodies associated with glycogenin-1 deficiency in skeletal muscle. Neuropathol Appl Neurobiol. 2024;50(3):e12995. Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, Das K, Toy T, Harry B, Yourshaw M, Fox M, Fogel BL, Martinez-Agosto JA, Wong DA, Chang VY, Shieh PB, Palmer CG, Dipple KM, Grody WW, Vilain E, Nelson SF. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA. 2014;312(18):1880–7. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM. Clinical whole-exome sequencing for the diagnosis of Mendelian disorders. N Engl J Med. 2013;369(16):1502–11. Ankala A, da Silva C, Gualandi F, Ferlini A, Bean LJ, Collins C, Tanner AK, Hegde MR. A comprehensive genomic approach for neuromuscular diseases gives a high diagnostic yield. Ann Neurol. 2015;77(2):206–14. Tables Table-1. Comprehensive table summarizing the clinical phenotypes and RBCK1 gene variants associated with Polyglucosan body myopathy (PGBM1) reported up to 2025 Case study Nucleotide change Amino acid change Variant position Variant type Sex Age of onset (years) Initial presentation Skeletal muscle Boisson et.al. (2012) Deletion Exon1- 4 c.553C>T -- p.Gln185* E1- 4, N E5, M Exon deletion Nonsense Female T -- p.Gln185* E1- 4, N E5, M Exon deletion Nonsense Female < 1 Infectious inflammation Myopathy Boisson et al. (2012) c.121_122 delCT p.L41fsX7 E2, N Frame shift Male T c.1160A>G p.Glu243* p.Asn387Ser E6, M E9, M Truncation Missense Female 12 Weakness in the leg Wheelchair Nilsson et al. (2013) c.727G>T c.1160A>G p.Glu243* p.Asn387Ser E6, M E9, M Nonsense Missense Female 16 Weakness in the leg Walked with aid Nilsson et al. (2013) c.896_899delAGTG p.Glu299Valfs*18 E7, M Frame shift Female 6 Weakness in the legs Walked Nilsson et al. (2013) c.896_899delAGTG p.Glu299Valfs*18 E7, M Frame shift Male 5 Running weakness Walked with aid Nilsson et al. (2013) c.722delC p.Ala241Glyfs*34 E6, M Frame shift Female NA Running weakness NA Nilsson et al. (2013) c.52G>C p.Ala18Pro E2, N Missense Male NA NA Walked with aid Nilsson et al. ( 2013) c.727_728InsGGCG Deletion Exon 1-4 p.Glu243Glyfs*114 -- E6, M E1-4 Frame shift Exon deletion Male 4 Running weakness Wheelchair Nilsson et al. ( 2013) c.1054C>T p.Arg352* E9, M Nonsense Male 12 Weakness in the legs NA Nilsson et al. (2013) c.917 + 3_917 + 4insG p.Arg298Argfs*40 E7, M Frame shift Female 17 Weakness in the legs Myopathy Nilsson et al. (2013) c.494delG p.Arg165Argfs*111 E5, M Frame shift Male 9 Running weakness Walked with aid Wang et al. (2013) c.570delC c.790C>T p.Pro190fs p.Gln222* E5, M E6, M Frame shift Nonsense Male 8 Myasthenia NA Wang et al. (2013) c.570delC c.790C>T p.Pro190fs p.Gln222* E5, M E6, M Frame shift Truncation Female 8 Myasthenia NA Wang et al. (2013) c.456 + 1G>C − E5, M Splicing variant NA NA Myasthenia NA Krenn et al. (2018) c.896_899del p. p.Glu299Valfs*46 E7, M Frame shift Female 14 Dyspnea Walked with aid Krenn et al. (2018) c.896_899del p.Glu299Valfs*46 E7, M Frame shift Female 12 Dyspnea Wheelchair Phadke et al., (2020) c.691delC p.Gln231Serfs*45 E6, M Frame shift Female <3 Delayed motor development Walked with aid Phadke et al. (2020) c.691delC p.Gln231Serfs*45 E6, M Female T c.1522_1526del p.Gln267* p.Asn508Profs*4 E7,M E12, C Nonsense Frame shift Male 9 Abdominal pain Walked limited Phadke et al. (2020) c.817dupC c.1465delA p.Leu273Profs*27 p.Thr489Profs*9 E7, M E12,C Frame shift Frame shift Male 4 Weakness in the legs Wheelchair Chen et al. (2021) c.1411G>A p.Glu471Lys E7, M Missense Male 13 Weakness in the legs Difficulty walking AlAnzi et al. (2022) c.913 T>C p.Cys305Arg E7, M Missense Female, 3.5 Exercise intolerance, liver enlargement Intolerant to exercise Sun et al. (2024) c.919G>T c.723_730dup p. Glu307* p. Glu244fs E7, M Nonsense Frame shift Male 15 Infectious inflammation Difficulty walking Table-2. Summary with outcomes of the haematological and biochemical parameters based investigations of blood Haematological Parameters Hb 14.1g/dL 11-15 g/dL MCV 80 fL 80-100 fL MCH 35 pg 27-32 pg Total Leucocyte Count 12000/m 3 4000-11000/m 3 Differential Leucocyte Count N74L20 Platelet Count 3,06,000/m 3 150000-450000 Biochemical parameters Aspartate Transferase 45U/L 10-40U/L Alanine Transferase 31U/L 10-40U/L Alkaline Phosphate 207 U/L <240 U/L Total Bilirubin 0.7 mg/dL 0.2-1.2 mg/dL Direct Bilirubin 0.5 mg/dL 0.01-0.3 mg/dL Indirect bilirubin 0.2 mg/dL 0.2-0.8 mg/dL Total Protein 7.1 g/dL 6.4-8.5 g/dL Serum Albumin 3.9 g/dL 3.2-5.5 g/dL Urea 38 mg/dL 15-45 mg/dL Creatinine 0.5 mg/dL 0.5-1.4 mg/dL Sodium/Potassium 130/3.9 mmol/L 135-145/3.5-5.5 mmol/L Calcium 9.3 mg/dL 8.6-10.3 mg/dL Phosphorus 4.2 mg/dL 2.5-4.5 mg/dL Creatinine PhosphoKinase 212 U/L 26-140 U/L Lactate Dehydrogenase 742 U/L 240-480 U/L TC/TG/HDL/LDL/VLDL (mg/dL) 126/100/50/80/20 - T3 63 80-200ng/dL T4 7 5-12 µg/dL TSH 20 0.4-4.0mIU/L HbA1c 6.1% <5.7% Viral Markers Negative - Table-3. Summary with outcomes of the immunological and cardiac profile as well as imaging based investigations Immunological profile ANA Negative <1:40 ANCA Negative <3.0IU/ml Erythrocyte Sedimentation Rate (ESR) 05 mm in 1 st hour Quantitative C-Reactive Protein (qCRP) 03 mg/L Cardiac Profile Troponin I <1.0 CK MB 5.0 Brain Natriuretic Peptide 508 Nerve Conduction Study Normal (MNCS and SNCS) Electromyography Myogenic pattern Imaging 2D ECHO Global hypokinesia, Ejection Fraction – 40% Ultrasound whole abdomen Bilateral moderate pleural effusion and moderate ascitis B/L Renal artery Doppler Within normal limits MRI Thigh The obturator, gluteal, vastus, adductor, Sartorius, and graceless muscle groups appear spared. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8775190","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":590455839,"identity":"1e19c0c9-10d0-43a0-ac4a-8cd446e31fd8","order_by":0,"name":"Akansha Jain","email":"","orcid":"","institution":"Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi-221005(UP), INDIA,","correspondingAuthor":false,"prefix":"","firstName":"Akansha","middleName":"","lastName":"Jain","suffix":""},{"id":590455849,"identity":"137e2c19-20a5-4f6d-97a8-27a534990a71","order_by":1,"name":"Niraj Kumar Srivastava","email":"","orcid":"","institution":"Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi-221005(UP), INDIA,","correspondingAuthor":false,"prefix":"","firstName":"Niraj","middleName":"Kumar","lastName":"Srivastava","suffix":""},{"id":590455850,"identity":"8e4afc23-cbe7-42e0-86e3-3894c2a5e62c","order_by":2,"name":"Sanchit Shailendra Chouksey","email":"","orcid":"","institution":"Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi-221005(UP), INDIA,","correspondingAuthor":false,"prefix":"","firstName":"Sanchit","middleName":"Shailendra","lastName":"Chouksey","suffix":""},{"id":590455851,"identity":"2aa02225-e200-4f77-956f-c260bae99ece","order_by":3,"name":"Nayana Bhuyan","email":"","orcid":"","institution":"Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi-221005(UP), INDIA,","correspondingAuthor":false,"prefix":"","firstName":"Nayana","middleName":"","lastName":"Bhuyan","suffix":""},{"id":590455852,"identity":"c04fc191-2026-4506-ab9f-0f078de4fe47","order_by":4,"name":"Arpan Mitra","email":"","orcid":"","institution":"Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi-221005(UP), INDIA,","correspondingAuthor":false,"prefix":"","firstName":"Arpan","middleName":"","lastName":"Mitra","suffix":""},{"id":590455853,"identity":"7b36f014-92a8-4aec-b186-0b1bde4aaa0d","order_by":5,"name":"Shreya Garg","email":"","orcid":"","institution":"Interventional Radiology and Endovascular Therapies NH-Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata- 700099 (WB), INDIA.","correspondingAuthor":false,"prefix":"","firstName":"Shreya","middleName":"","lastName":"Garg","suffix":""},{"id":590455854,"identity":"a0d46c5b-a0d5-4766-a2d7-1f9a2efa8a8f","order_by":6,"name":"Vijaya Nath Mishra","email":"","orcid":"","institution":"Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi-221005(UP), INDIA,","correspondingAuthor":false,"prefix":"","firstName":"Vijaya","middleName":"Nath","lastName":"Mishra","suffix":""},{"id":590455855,"identity":"3992a291-40d9-4668-ac72-558215ff24b5","order_by":7,"name":"Abhishek Pathak","email":"data:image/png;base64,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","orcid":"","institution":"Institute of Medical Sciences (IMS), Banaras Hindu University (BHU), Varanasi-221005(UP), INDIA,","correspondingAuthor":true,"prefix":"","firstName":"Abhishek","middleName":"","lastName":"Pathak","suffix":""}],"badges":[],"createdAt":"2026-02-03 11:38:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8775190/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8775190/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103587211,"identity":"00134373-fd36-4636-842b-5a7bb5df6670","added_by":"auto","created_at":"2026-02-27 11:27:27","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47713,"visible":true,"origin":"","legend":"\u003cp\u003eThe pedigree chart indicates consanguinity marriage, with both parents originating from the same familial ancestry. They have three surviving children. Among them are two older non-twin siblings, a boy and a girl, and a set of opposite-sex fraternal twins. The male twin passed away in infancy, while his twin sister, who survived, has been diagnosed with Polyglucosan Body Myopathy-1 (PGBM-1) due to a homozygous pathogenic mutation in the RBCK1 gene.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8775190/v1/340375fce4b82eb648d9c4ab.jpg"},{"id":103587192,"identity":"47a40caa-4603-4830-ad3f-27e3c910e38e","added_by":"auto","created_at":"2026-02-27 11:27:23","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":84383,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA.\u003c/strong\u003e Axial PD Fat-Saturated image of the left thigh and \u003cstrong\u003eB.\u003c/strong\u003e Coronal T2 STIR image of the bilateral thighs demonstrate mild, diffuse hyperintensity within the affected muscle fibers. The involved muscle groups are indicated by colored arrows: Orange arrow – Obturator muscles; Blue arrow – Gluteal muscles; Yellow arrow – Vastus muscles; Red arrow – Adductor muscles. Muscles spared include the Sartorius (blue circle) and Gracilis (green circle). \u003cstrong\u003eC.\u003c/strong\u003e Axial PD Fat-Saturated image of the left thigh and \u003cstrong\u003eD.\u003c/strong\u003e Coronal T2 STIR image of the bilateral thighs again show mild, diffuse hyperintensity within the affected muscle fibers (arrows).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8775190/v1/66a08af8b782aa82cd9453b8.jpg"},{"id":103587194,"identity":"01ea7ad1-6b26-464b-986d-c054f1f4bd9e","added_by":"auto","created_at":"2026-02-27 11:27:23","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":3520714,"visible":true,"origin":"","legend":"\u003cp\u003eThe EMG pattern showed predominantly small-amplitude motor unit potentials (approximately 50 µV per division) with short durations (10 ms/cm), along with an increased proportion of polyphasic MUPs. All patients demonstrated early recruitment and a mixed interference pattern.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8775190/v1/e0e9be762e8610bb791ae991.jpg"},{"id":103587256,"identity":"68e5143a-8107-4925-823a-cae2fb592495","added_by":"auto","created_at":"2026-02-27 11:27:37","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":138097,"visible":true,"origin":"","legend":"\u003cp\u003eRBCK1 variants were identified in both the patient and her parents. The patient was found to carry heterozygous variants in the RBCK1 gene, inherited from each parent. Specifically, a deletion of the nucleotide sequence \u003cstrong\u003eCCTG \u003c/strong\u003eat position \u003cstrong\u003ec.635_638\u003c/strong\u003ewas detected in the RBCK1 gene.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8775190/v1/479e49a600a51a80a2dc8edc.jpg"},{"id":103587186,"identity":"15c76a27-5c7c-4fcd-9fd3-468eedf7876a","added_by":"auto","created_at":"2026-02-27 11:27:21","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":112554,"visible":true,"origin":"","legend":"\u003cp\u003ePathophysiology based mechanistic route of mutation due to RBCK1 gene is presented. Mutations in RBCK1 cause a breakdown in linear ubiquitination, impairing NF-κB–mediated immune signaling. This causes a spectrum of clinical phenotypes ranging from immunodeficiency and auto-inflammation\u003cstrong\u003e to \u003c/strong\u003eprogressive muscular and cardiac pathology\u003cstrong\u003e,\u003c/strong\u003edepending on the mutation type and residual LUBAC activity.\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8775190/v1/361e5c514e62e6dc317bfd50.jpg"},{"id":108691500,"identity":"39f79c94-1d9c-46bb-a7c8-ab10179bb7b8","added_by":"auto","created_at":"2026-05-07 10:57:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4328104,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8775190/v1/3c64d0b9-18a8-4db0-acdc-4bbf3f10e089.pdf"},{"id":103587205,"identity":"23390494-cef2-42a1-8ad2-4f1f377eed1a","added_by":"auto","created_at":"2026-02-27 11:27:25","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":127053,"visible":true,"origin":"","legend":"","description":"","filename":"NCVINVESTIGATION.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8775190/v1/6228998d303f06db7a599e8d.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical, Neurological, and Genetic Characterization of Polyglucosan Body Myopathy Type 1 (PGBM1) in a Pediatrics Patient: Expanding the Spectrum of RBCK1-Related Disorders","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePolyglucosan body myopathy type 1 (PGBM1) is a rare genetic disorder caused by homozygous or compound heterozygous mutations in the RBCK1 gene, which encodes the E3 ubiquitin ligase RBCK1 (also known as HOIL-1). This protein is a crucial component of the linear ubiquitin chain assembly complex (LUBAC), and its dysfunction disrupts LUBAC activity [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. As a result, insoluble, glycogen-like Polyglucosan bodies accumulate in tissues, highlighting a pathological connection between impaired ubiquitination and abnormal glycogen metabolism. While the age of onset in PGBM1 varies, childhood presentation is relatively rare and often clinically diverse. Early-onset forms typically involve prominent skeletal muscle weakness, especially in proximal limb, neck, facial, and truncal muscles, as well as systemic manifestations such as juvenile-onset cardiomyopathy and immune dysregulation [\u003cspan additionalcitationids=\"CR7 CR8 CR9\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA literature search using the keywords \u0026ldquo;Polyglucosan body myopathy 1,\u0026rdquo; \u0026ldquo;PGBM1,\u0026rdquo; and \u0026ldquo;RBCK1 gene\u0026rdquo; was conducted via the National Centre for Biotechnology Information (NCBI) and PubMed databases (as of March 2025), yielding nine relevant reports. Across these studies, 25 PGBM1 patients with RBCK1 variants were identified. The reported variants included frame shift, nonsense, missense, large fragment deletions, and splice site mutations, with frame shift variants being the most frequently observed (Table\u0026nbsp;1). Among the 25 patients, 16 experienced proximal muscle weaknesses, 4 presented with recurrent infections, and 3 had dyspnea. Myocardial involvement was reported in 21 patients, and skeletal muscle involvement in 19. Notably, 4 patients with RBCK1 N-terminal variants initially presented with infections, while 21 patients with C-terminal or intermediate region variants commonly showed proximal muscle weakness and cardiomyopathy, reported in 21 and 20 cases, respectively. Additionally, 8 patients with loss-of-function RBCK1 variants (nonsense, frame shift, or large fragment deletions) died during the disease course [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition to all the above-described studies, we are going to add a rare and unusual case presentation of PGBM-1. Our case will enrich the medical literature in the context of diagnosis, prognosis, the row of all the above-described studies; we are also going to add a rare and unusual case presentation of PGBM-1. Our case is going to enrich the medical literature in the context of the diagnosis, prognosis and management.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eClinical and Neurological Evaluation\u003c/h2\u003e \u003cp\u003eA 17-year-old female was evaluated for gradually progressive, symmetrical proximal muscle weakness that began at eight years of age. The initial symptoms included exercise intolerance, calf pain, and frequent falls due to knee buckling during short-distance running. Progressively, she experienced difficulty climbing stairs, rising from a seated position, toe walking, turning in bed, wearing shirts, and pouring water overhead. Facial involvement was noted with difficulty sucking through straws, blowing out candles, and bilateral eyelid drooping.\u003c/p\u003e \u003cp\u003eOver the past two years, she developed exertional dyspnea [New York Heart Association (NYHA) Grade I], which progressed to Grade IV in the previous year, along with orthopnea and paroxysmal nocturnal dyspnea. No chest pain was reported.\u003c/p\u003e \u003cp\u003eShe was the third-born child of a consanguineous marriage (third-degree relatives) and part of a twin birth; her twin brother died shortly after birth due to respiratory distress. There was no similar illness in other family members. Pedigree analysis confirmed consanguinity in the second generation (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Development was normal until age 10, after which she developed stunted growth, poor weight gain, and short stature. Early menarche occurred at age 9, followed by secondary amenorrhea from age 11.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePhysical and Neurological Examination\u003c/h3\u003e\n\u003cp\u003eOn examination, the patient was thin and undernourished (BMI 12.6), with height and weight below age-appropriate percentiles. She had generalized muscle wasting and bilateral scapular winging. Higher mental functions were normal (MMSE 26/30). Cardiovascular examination revealed raised jugular venous pressure, bilateral pitting pedal edema, moderate ascites with shifting dullness, and a grade 3 pansystolic murmurs over mitral and tricuspid areas. The apex beat was displaced to the 6th intercostal space, lateral to the midclavicular line, suggesting cardiomegaly. Respiratory examination showed bilateral basal crepitations and reduced chest expansion (3 cm).\u003c/p\u003e \u003cp\u003eNeurologically, she exhibited bilateral lower motor neuron-type facial weakness with bilateral ptosis, sparing pupils, extraocular, pharyngeal, and respiratory muscles. Peripheral nerve and cerebellar functions were intact. Motor examination revealed generalized atrophy with preserved tone, symmetrical proximal weakness in upper (shoulder, elbow) and lower limbs (hip, knee), positive Gower\u0026rsquo;s sign, and neck/truncal weakness.\u003c/p\u003e\n\u003ch3\u003eInvestigations\u003c/h3\u003e\n\u003cp\u003eRoutine blood tests (complete blood count, liver, and renal function) were normal. Thyroid function tests revealed elevated TSH (20 U/L) with low T3 and low-normal T4, consistent with primary hypothyroidism. Creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) levels were elevated (Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e2D echocardiography demonstrated global hypokinesia and an ejection fraction of 40%, consistent with dilated cardiomyopathy. MRI of both thighs showed mild diffuse hyperintensity within affected muscle fibers, sparing the obturator, gluteal, vastus, adductor, sartorius, and gracilis groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;3). Nerve conduction studies were normal, whereas electromyography revealed a myopathic pattern in all four limbs (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Ultrasonography of the thorax and abdomen showed bilateral moderate pleural effusion and moderate ascites without structural cardiac anomalies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eGenetic Analysis\u003c/h3\u003e\n\u003cp\u003eWhole-exome sequencing (WES) was performed to identify the underlying genetic cause. A homozygous frameshift mutation in exon 6 of the RBCK1 gene (chr20: g.419607_419610delCTGG; c.635_638delGCTG) was detected, resulting in a frameshift starting at codon 212 and producing a premature stop codon (p.Gly212Valfs*63). Sanger sequencing confirmed the presence of this homozygous variant in the proband and heterozygosity in both parents, consistent with autosomal recessive inheritance.\u003c/p\u003e \u003cp\u003eIn silico prediction tools classified p.Gly212Valfs*63 as a loss-of-function (LoF) variant in RBCK1, a gene intolerant to LoF mutations. The variant was absent in population databases such as gnomAD and internal variant repositories, confirming its novel pathogenicity (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eClinical evaluation revealed a progressive proximal myopathy predominantly affecting the lower limbs, with gradual involvement of the upper limbs. The onset of symptoms was noted in early childhood, characterized initially by exercise intolerance, difficulty in running, frequent falls due to knee buckling, and progressive difficulty in climbing stairs and rising from a seated position. Over the years, the weakness advanced symmetrically, resulting in a waddling gait and reliance on support for ambulation. There were no bulbar, respiratory, or sensory symptoms, and the patient\u0026rsquo;s cognitive functions remained intact.\u003c/p\u003e \u003cp\u003eSystemic evaluation identified mild cardiomyopathy on echocardiography, characterized by left ventricular systolic dysfunction (ejection fraction 45%), without conduction abnormalities or arrhythmias on ECG. Endocrine assessment revealed hypothyroidism (elevated TSH with low free T4), for which thyroid hormone replacement therapy was initiated. Notably, there was no clinical or laboratory evidence of immune dysfunction\u0026mdash;the patient had no history of recurrent infections, inflammatory lesions, or autoimmunity. Furthermore, hepatosplenomegaly was absent on abdominal ultrasonography, ruling out systemic organ involvement.\u003c/p\u003e \u003cp\u003eMagnetic resonance imaging (MRI) of the thigh and pelvic muscles demonstrated a characteristic pattern of selective muscle involvement. The gluteus maximus, semitendinosus, semimembranosus, and adductor magnus muscles showed hyperintensity on T1-weighted and T2-FLAIR images, suggesting fatty infiltration and atrophy, whereas the rectus femoris, sartorius, and gracilis muscles were relatively preserved. This pattern was consistent with chronic myopathic changes commonly reported in Polyglucosan Body Myopathy Type 1 (PGBM1).\u003c/p\u003e \u003cp\u003eElectrophysiological studies revealed a myopathic pattern on needle electromyography (EMG), characterized by small amplitude, short-duration motor unit potentials with early recruitment, while nerve conduction studies were within normal limits, confirming a primary myopathic process rather than neuropathic involvement.\u003c/p\u003e \u003cp\u003eGenetic analysis using whole-exome sequencing identified a novel homozygous frameshift mutation in the RBCK1 gene (c.635_638delGCTG; p.Gly212Valfs*63), leading to a premature truncation of the HOIL-1 protein. Both parents were found to be heterozygous carriers of the same variant upon segregation analysis, consistent with autosomal recessive inheritance. The identified variant was not reported in population databases (gnomAD, ExAC) and was predicted to result in loss of function due to nonsense-mediated mRNA decay or truncated non-functional protein.\u003c/p\u003e \u003cp\u003eThis novel mutation expands the known genotypic spectrum of RBCK1-related disorders. Unlike previously reported cases showing a triad of myopathy, cardiomyopathy, and immune dysfunction, the present case demonstrated a muscle-predominant phenotype with cardiomyopathy and endocrine abnormalities (hypothyroidism) but without immune or hepatic involvement. This highlights a distinct clinical subtype within the RBCK1-associated disease continuum.\u003c/p\u003e \u003cp\u003eOverall, the combination of clinical presentation, muscle MRI pattern, EMG findings, muscle biopsy histopathology, and confirmatory molecular diagnosis established Polyglucosan Body Myopathy Type 1 (PGBM1) due to a novel homozygous RBCK1 frameshift mutation (c.635_638delGCTG; p.Gly212Valfs*63), thereby contributing to the expanding phenotypic and genotypic spectrum of this rare disorder.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRBCK1 mutations are rare and exhibit diverse clinical phenotypes, including primary immune deficiencies and neuromuscular disorders such as Polyglucosan body myopathy. Polyglucosan is an abnormally structured form of glycogen that is poorly branched and resistant to degradation by α-amylase [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. When viewed under an electron microscope, it displays a characteristic fibrous appearance. Due to its reduced branching, Polyglucosan tends to aggregate into compact inclusion bodies known as Polyglucosan bodies. While small amounts of polyglucosan can accumulate in various tissues under normal physiological conditions, excessive accumulation is indicative of disorders related to glycogen metabolism. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. One such condition is PGBM1, a glycogen storage disease marked by the pathological build-up of Polyglucosan in tissues [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The disease can present at any age, from infancy to adolescence, and typically manifests as progressive weakness in the proximal muscles, eventually leading to walking difficulties. Most affected individuals also develop progressive dilated cardiomyopathy, which may necessitate heart transplantation in severe cases. In a minority of patients, the disease also causes significant immune deficiency and heightened inflammation during early childhood [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The present case involves a 17-year-old girl who demonstrated gradually progressive, symmetrical proximal muscle weakness and exercise intolerance since childhood, features characteristic of RBCK1-associated myopathy. However, this case stands out due to its additional, atypical clinical manifestations. Among the most striking features was the onset of precocious puberty at 9 years, followed by secondary amenorrhea at 11 years, suggesting early disruption of endocrine regulation potentially linked to the RBCK1 mutation. Mutation of RBCK1 gene is found novel in our case also enrich the literature with a new finding. The mutation is observed on exome-6 and also a frame-shift mutation. Such mutation is responsible for muscular weakness [\u003cspan additionalcitationids=\"CR13 CR14 CR15\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Supporting this, she exhibited endocrine abnormalities, including markedly elevated thyroid-stimulating hormone levels, consistent with clinical hypothyroidism. Poor weight gain, short stature, and growth failure post age 10 further point to systemic involvement, implicating RBCK1's role in metabolic and endocrine pathways. All these things also overlapped with the previously reported cases [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeurologically, the patient had bilateral lower motor neuron facial weakness, ptosis with sparing of pupils and extraocular muscles, and generalised proximal muscle weakness without specific muscle group predilection. All these findings, along with electromyographic confirmation of a myopathic pattern and normal nerve conduction studies, support a primary myopathic disorder. In the context of RBCK1\u0026rsquo;s function in ubiquitination and cellular proteostasis, its mutation likely contributes to progressive muscle fibre degeneration and weakness [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCardiac evaluation revealed NYHA class IV dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and dilated cardiomyopathy with an ejection fraction of 40%, all indicating significant cardiac involvement. Additional findings of bilateral pleural effusions and ascites were consistent with heart failure and suggest decompensation secondary to the cardiomyopathy. Cardiac manifestations like these are recognised complications in various myopathies and significantly affect prognosis [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe coexistence of myopathy, dilated cardiomyopathy, and endocrinopathy necessitates the consideration of differential diagnoses, including mitochondrial myopathies, limb-girdle muscular dystrophies, and glycogen storage diseases. However, the confirmed autosomal recessive RBCK1 mutation identified through whole-exome sequencing in the patient and both of her parents, along with the matching clinical phenotype, supports a definitive diagnosis [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10 CR11\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the light of all above descriptions and literature reviews, we have a pathophysiological overview. This overview is represented by figure-5. RBCK1/HOIL-1 is a non-catalytic yet crucial component of the LUBAC complex, necessary for both the assembly of Met1-linked ubiquitin chains and the regulation of their activity through distinct ester-linked ubiquitination. By mediating linear ubiquitination of NF-κB signalling regulators, it ensures balanced inflammatory responses, antiviral immunity, and cell survival. Disease-causing variants in RBCK1 highlight the intricate relationship between ubiquitin-mediated signalling and the development of immunological and muscular disorders in humans [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNotably, features such as precocious puberty, secondary amenorrhea, coarse facies, bilateral ptosis, and facial weakness are rarely described in RBCK1-related disorders, suggesting an expanded phenotypic spectrum that may include endocrine and craniofacial involvement. This case underscores the importance of a thorough systemic evaluation in individuals with RBCK1 mutations, given the potential for multisystem involvement and novel clinical features [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis case highlights the critical role of genetic testing in the assessment of complex neuromuscular disorders. Identifying a mutation in the RBCK1 gene not only establishes a definitive molecular diagnosis but also supports informed family counselling due to its autosomal recessive inheritance. Early diagnosis can influence clinical management by enabling proactive monitoring for cardiopulmonary complications and implementing personalised endocrine therapies. These findings highlight the importance of recognising rare genetic myopathies and their systemic involvement to promote timely diagnosis and intervention. Continued research into the function of RBCK1 in cardiac and endocrine systems may further illuminate its underlying pathophysiological mechanisms. In the context of the rarity and phenotypic variability of PGBM, this case underscores several key areas that merit deeper investigation. Large-scale genomic and whole-exome sequencing studies are needed to identify novel genetic variants associated with PGBM. Functional validation of these variants will be crucial for elucidating genotype-phenotype correlations and uncovering the underlying pathomechanisms, particularly in atypical or adult-onset cases. There is an urgent need for reliable, non-invasive biomarkers, ideally serum-based or imaging-derived to facilitate early and differential diagnosis. Advanced neuroimaging techniques like MR spectroscopy or PET imaging may provide additional diagnostic insights, particularly during subclinical stages. Future research should also prioritize the quantitative assessment of Polyglucosan inclusion bodies, their distribution across tissues, and their association with muscle fibre types and neurogenic atrophy. Studies employing animal models or in vitro systems can further elucidate the cellular mechanisms driving Polyglucosan body accumulation, including potential autophagy, glycogen metabolism, or mitochondrial function disruptions. The development of standardized diagnostic criteria encompassing clinical, histopathological, biochemical, and genetic parameters will be instrumental in promoting early and accurate diagnosis. Creating international registries and longitudinal databases will also support epidemiological studies and enhance our understanding of disease progression. Currently, treatment remains largely supportive. Future therapeutic directions may include gene therapy or CRISPR-based correction of pathogenic mutations, enzyme replacement or chaperone therapies targeting glycogen metabolism, and the repurposing of existing drugs or nutraceuticals to enhance autophagy or reduce Polyglucosan accumulation. In the context of potential overlap with other neuromuscular disorders, a multidisciplinary approach involving neurologists, geneticists, physiotherapists, and metabolic specialists is essential. Research into the effectiveness of rehabilitation strategies, physiotherapy, and assistive technologies in preserving functional independence is also vital. Finally, longitudinal studies focusing on quality of life, disease trajectory, and psychosocial impact will be important to delivering patient-centred care and improving long-term outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePGBM1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolyglucosan Body Myopathy Type 1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRBCK1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRanBP-type and C3HC4-type zinc finger-containing protein 1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNGS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNext-Generation Sequencing\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAutosomal Recessive.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics Approval\u003c/strong\u003e \u003cp\u003eEthical approval was not required for this single case report as per the institutional ethics committee policy.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to Participate\u003c/strong\u003e \u003cp\u003eInformed consent for participation in clinical management and data collection was obtained from the patient\u0026rsquo;s next \u003cb\u003eof kin.\u003c/b\u003e\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eWritten Consent for Publication\u003c/h2\u003e \u003cp\u003e Written informed consent for publication of this case and accompanying images was obtained from the patient\u0026rsquo;s legally authorized representative. A copy of the consent form is available for review by the journal\u0026rsquo;s editorial office upon request.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNil. No financial support was received for this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA.J., N.K.S. and S.S.C. contributed significantly to the conception and design of the study, reviewed and revised the manuscript for intellectual content, and approved the final version before submission. N.V. and A.M. were involved in the review and editing of the manuscript. S.G. was involved in the analysis. V.N.M. edited and reviewed the manuscript. A.P. was involved in the supervision, final review and editing. All authors were approved the final manuscript and consented to authorship.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe sincerely thank for parents of patient to provide the permission of clinical data, which has been invaluable to our study. We deeply appreciate their willingness to share personal medical information to advance clinical understanding and improve future patient care.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e \u003cp\u003eAll data supporting the findings of this case report, including anonymized clinical details, imaging studies, and genetic test results, are available from the corresponding author upon reasonable request. No publicly available datasets were generated or analyzed during the current study. The data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\u003ch2\u003eCode Availability\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAlAnzi T, Al Harbi F, AlGhamdi A, Mohamed S. A novel variant of RBCK1 gene causes mild polyglucosan myopathy. Neurosciences (Riyadh). 2022;27(1):45\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoisson B, Laplantine E, Dobbs K, Cobat A, Tarantino N, Hazen M, Lidov HG, Hopkins G, Du L, Belkadi A, Chrabieh M, Itan Y, Picard C, Fournet JC, Eibel H, Tsitsikov E, Pai SY, Abel L, Al-Herz W, Casanova JL, Israel A, Notarangelo LD. Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia. J Exp Med. 2015;212(6):939\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen L, Wang N, Hu W, Yu X, Yang R, Han Y, Yan Y, Nian N, Sha C. Polyglucosan body myopathy 1 may cause cognitive impairment: a case report from China. BMC Musculoskelet Disord. 2021;22(1):35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFujita H, Rahighi S, Akita M, Kato R, Sasaki Y, Wakatsuki S, Iwai K. Mechanism underlying IκB kinase activation mediated by the linear ubiquitin chain assembly complex. Mol Cell Biol. 2014;34(7):1322\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHedberg-Oldfors C, Oldfors A. Polyglucosan storage myopathies. Mol Aspects Med. 2015;46:85\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBoisson B, Laplantine E, Prando C, Giliani S, Israelsson E, Xu Z, Abhyankar A, Isra\u0026euml;l L, Trevejo-Nunez G, Bogunovic D, Cepika AM, MacDuff D, Chrabieh M, Hubeau M, Bajolle F, Debr\u0026eacute; M, Mazzolari E, Vairo D, Agou F, Virgin HW, Bossuyt X, Rambaud C, Facchetti F, Bonnet D, Quartier P, Fournet JC, Pascual V, Chaussabel D, Notarangelo LD, Puel A, Isra\u0026euml;l A, Casanova JL, Picard C. Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency. Nat Immunol. 2012;13(12):1178\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrenn M, Salzer E, Simonitsch-Klupp I, Rath J, Wagner M, Haack TB, Strom TM, Sch\u0026auml;nzer A, Kilimann MW, Schmidt RLJ, Schmetterer KG, Zimprich A, Boztug K, Hahn A, Zimprich F. Mutations outside the N-terminal part of RBCK1 may cause polyglucosan body myopathy with immunological dysfunction: expanding the genotype\u0026ndash;phenotype spectrum. J Neurol. 2018;265(2):394\u0026ndash;401.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNilsson J, Schoser B, Laforet P, Kalev O, Lindberg C, Romero NB, D\u0026aacute;vila L\u0026oacute;pez M, Akman HO, Wahbi K, Iglseder S, Eggers C, Engel AG, DiMauro S, Oldfors A. Polyglucosan body myopathy caused by defective ubiquitin ligase RBCK1. Ann Neurol. 2013;74(6):914\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhadke R, Hedberg-Oldfors C, Scalco RS, Lowe DM, Ashworth M, Novelli M, Vara R, Merwick A, Amer H, Sofat R, Sugarman M, Jovanovic A, Roberts M, Nakou V, King A, Bodi I, Jungbluth H, Oldfors A, Murphy E. RBCK1-related disease: a rare multisystem disorder with polyglucosan storage, autoinflammation, recurrent infections, skeletal, and cardiac myopathy. J Inherit Metab Dis. 2020;43(5):1002\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobitaille Y, Carpenter S, Karpati G, DiMauro SD. A distinct form of adult polyglucosan body disease with massive involvement of central and peripheral neuronal processes and astrocytes. Brain. 1980;103(2):315\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang K, Kim C, Bradfield J, Guo Y, Toskala E, Otieno FG, Hou C, Thomas K, Cardinale C, Lyon GJ, Golhar R, Hakonarson H. Whole-genome DNA/RNA sequencing identifies truncating mutations in RBCK1 in a novel Mendelian disease with neuromuscular and cardiac involvement. Genome Med. 2013;5(7):67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun Q, Xie Z, Song L, Fu D. A case of polyglucosan body myopathy caused by an RBCK1 gene variant and literature review. Mol Genet Genom Med. 2024;12(4):e2432.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVisuttijai K, Hedberg-Oldfors C, Costello DJ, Bermingham N, Oldfors A. Proteomic profiling of polyglucosan bodies associated with glycogenin-1 deficiency in skeletal muscle. Neuropathol Appl Neurobiol. 2024;50(3):e12995.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, Das K, Toy T, Harry B, Yourshaw M, Fox M, Fogel BL, Martinez-Agosto JA, Wong DA, Chang VY, Shieh PB, Palmer CG, Dipple KM, Grody WW, Vilain E, Nelson SF. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA. 2014;312(18):1880\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, Bekheirnia MR, Leduc MS, Kirby A, Pham P, Scull J, Wang M, Ding Y, Plon SE, Lupski JR, Beaudet AL, Gibbs RA, Eng CM. Clinical whole-exome sequencing for the diagnosis of Mendelian disorders. N Engl J Med. 2013;369(16):1502\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnkala A, da Silva C, Gualandi F, Ferlini A, Bean LJ, Collins C, Tanner AK, Hegde MR. A comprehensive genomic approach for neuromuscular diseases gives a high diagnostic yield. Ann Neurol. 2015;77(2):206\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable-1.\u003c/strong\u003e Comprehensive table summarizing the clinical phenotypes and RBCK1 gene variants associated with Polyglucosan body myopathy (PGBM1) reported up to 2025\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"718\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCase study\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNucleotide change\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAmino acid change\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariant\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eposition\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariant type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAge of onset\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInitial presentation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSkeletal muscle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eBoisson \u0026nbsp;et.al. (2012)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003eDeletion Exon1- 4 \u0026nbsp; \u0026nbsp; c.553C\u0026gt;T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003cp\u003ep.Gln185*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eE1- 4, N\u003c/p\u003e\n \u003cp\u003eE5, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eExon deletion\u003c/p\u003e\n \u003cp\u003eNonsense\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt; 1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eMyopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eBoisson et al. (2012)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003eDeletion\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Exon 1- 4 \u0026nbsp;c.553C\u0026gt;T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e--\u003c/p\u003e\n \u003cp\u003ep.Gln185*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eE1- 4, N\u003c/p\u003e\n \u003cp\u003eE5, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eExon deletion\u003c/p\u003e\n \u003cp\u003eNonsense\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt; 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eInfectious\u003c/p\u003e\n \u003cp\u003einflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eMyopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eBoisson et al. (2012)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.121_122\u003c/p\u003e\n \u003cp\u003edelCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.L41fsX7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE2, N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt; 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eNilsson et al. (2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.727G\u0026gt;T c.1160A\u0026gt;G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Glu243*\u003c/p\u003e\n \u003cp\u003ep.Asn387Ser\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE6, M\u003c/p\u003e\n \u003cp\u003eE9, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eTruncation\u003c/p\u003e\n \u003cp\u003eMissense\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eWeakness\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;in the leg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWheelchair\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eNilsson et al. (2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.727G\u0026gt;T c.1160A\u0026gt;G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Glu243*\u003c/p\u003e\n \u003cp\u003ep.Asn387Ser\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE6, M\u003c/p\u003e\n \u003cp\u003eE9, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eNonsense Missense\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003ctable border=\"0\" cellspacing=\"3\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 137px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"3\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 109px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eWeakness\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;in the leg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWalked with aid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eNilsson et al.\u003c/p\u003e\n \u003cp\u003e(2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.896_899delAGTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Glu299Valfs*18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE7, M\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eWeakness in the legs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWalked\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eNilsson et al. \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; (2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.896_899delAGTG\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Glu299Valfs*18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE7, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eRunning weakness\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;Walked with aid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eNilsson et\u0026nbsp;al.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; (2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.722delC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Ala241Glyfs*34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE6, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eRunning weakness\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eNilsson et\u0026nbsp;al.\u003c/p\u003e\n \u003cp\u003e(2013) \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.52G\u0026gt;C\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Ala18Pro\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE2, N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eMissense\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eNA\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWalked with aid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eNilsson et al. ( 2013)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.727_728InsGGCG\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDeletion Exon 1-4 \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Glu243Glyfs*114\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; --\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE6, M\u003c/p\u003e\n \u003cp\u003eE1-4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003cp\u003eExon deletion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eRunning weakness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWheelchair\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eNilsson et\u0026nbsp;al.\u003c/p\u003e\n \u003cp\u003e( 2013)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.1054C\u0026gt;T\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Arg352*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE9, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eNonsense\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eWeakness in the legs\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eNilsson et\u0026nbsp;al. (2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.917 + 3_917 + 4insG\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Arg298Argfs*40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE7, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eWeakness in the legs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eMyopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;Nilsson et al.\u003c/p\u003e\n \u003cp\u003e(2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.494delG\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Arg165Argfs*111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE5, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eRunning weakness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWalked with aid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eWang et\u0026nbsp;al. (2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.570delC\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ec.790C\u0026gt;T\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Pro190fs\u003c/p\u003e\n \u003cp\u003ep.Gln222*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE5, M\u003c/p\u003e\n \u003cp\u003eE6, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003cp\u003eNonsense\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eMyasthenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eWang et\u0026nbsp;al.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.570delC\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;c.790C\u0026gt;T \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Pro190fs\u003c/p\u003e\n \u003cp\u003ep.Gln222*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE5, M\u003c/p\u003e\n \u003cp\u003eE6, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003cp\u003eTruncation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eMyasthenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eWang et\u0026nbsp;al. (2013)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.456 + 1G\u0026gt;C \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003e\u0026minus;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE5, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eSplicing variant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eNA\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eMyasthenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eKrenn et\u0026nbsp;al. (2018)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.896_899del p.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Glu299Valfs*46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE7, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eDyspnea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWalked\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;with aid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eKrenn et al.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(2018)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.896_899del\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Glu299Valfs*46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE7, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eDyspnea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWheelchair\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003ePhadke et\u0026nbsp;al., (2020)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.691delC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Gln231Serfs*45\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE6, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eDelayed motor\u0026nbsp;\u003c/p\u003e\n \u003cp\u003edevelopment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWalked with aid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003ePhadke et\u0026nbsp;al. (2020)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.691delC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Gln231Serfs*45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE6, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eDifficulty breathing\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eand running\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWheelchair\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003ePhadke et al. (2020)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.799C\u0026gt;T c.1522_1526del\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Gln267*\u003c/p\u003e\n \u003cp\u003ep.Asn508Profs*4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE7,M\u003c/p\u003e\n \u003cp\u003eE12, C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eNonsense\u003c/p\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eAbdominal pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWalked limited\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003ePhadke et al. (2020)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.817dupC c.1465delA\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Leu273Profs*27\u003c/p\u003e\n \u003cp\u003ep.Thr489Profs*9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE7, M\u003c/p\u003e\n \u003cp\u003eE12,C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eWeakness in the legs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eWheelchair\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eChen et\u0026nbsp;al. (2021)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.1411G\u0026gt;A \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Glu471Lys\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE7, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eMissense\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eWeakness in the legs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eDifficulty walking\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eAlAnzi et\u0026nbsp;al. (2022)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.913 T\u0026gt;C\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 112px;\"\u003e\n \u003cp\u003ep.Cys305Arg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003eE7, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eMissense\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eFemale,\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eExercise intolerance,\u003c/p\u003e\n \u003cp\u003eliver enlargement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eIntolerant to exercise\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003eSun et al.\u003c/p\u003e\n \u003cp\u003e(2024)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003ec.919G\u0026gt;T\u003c/p\u003e\n \u003cp\u003ec.723_730dup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003ep. Glu307*\u003c/p\u003e\n \u003cp\u003ep. Glu244fs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 55px;\"\u003e\n \u003cp\u003eE7, M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003eNonsense\u003c/p\u003e\n \u003cp\u003eFrame shift\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 48px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eInfectious\u003c/p\u003e\n \u003cp\u003einflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003eDifficulty walking\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 80px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 108px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 112px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 1px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 55px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 52px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable-2.\u003c/strong\u003e Summary with outcomes of the haematological and biochemical parameters based investigations of blood\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHaematological Parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eHb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e14.1g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e11-15 g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eMCV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e80 fL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e80-100 fL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eMCH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e35 pg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e27-32 pg\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eTotal Leucocyte Count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e12000/m\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e4000-11000/m\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eDifferential Leucocyte Count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eN74L20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003ePlatelet Count\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e3,06,000/m\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e150000-450000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBiochemical parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eAspartate Transferase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e45U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e10-40U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eAlanine Transferase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e31U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e10-40U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eAlkaline Phosphate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e207 U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026lt;240 U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eTotal Bilirubin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e0.7 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e0.2-1.2 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eDirect Bilirubin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e0.5 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e0.01-0.3 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eIndirect bilirubin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e0.2 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e0.2-0.8 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eTotal Protein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e7.1 g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e6.4-8.5 g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eSerum Albumin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e3.9 g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e3.2-5.5 g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eUrea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e38 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e15-45 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eCreatinine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e0.5 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e0.5-1.4 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eSodium/Potassium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e130/3.9 mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e135-145/3.5-5.5 mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eCalcium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e9.3 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e8.6-10.3 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003ePhosphorus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e4.2 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e2.5-4.5 mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eCreatinine PhosphoKinase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e212 U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e26-140 U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eLactate Dehydrogenase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e742 U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e240-480 U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eTC/TG/HDL/LDL/VLDL (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e126/100/50/80/20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eT3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e80-200ng/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eT4\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e5-12 \u0026micro;g/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eTSH\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e0.4-4.0mIU/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eHbA1c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e6.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026lt;5.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eViral Markers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable-3.\u003c/strong\u003e Summary with outcomes of the immunological and cardiac profile as well as imaging based investigations\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImmunological profile\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eANA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026lt;1:40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eANCA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003e\u0026lt;3.0IU/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eErythrocyte Sedimentation Rate (ESR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003emm in 1\u003csup\u003est\u003c/sup\u003e hour\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eQuantitative C-Reactive Protein (qCRP)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 200px;\"\u003e\n \u003cp\u003emg/L\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCardiac Profile\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eTroponin I\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e\u0026lt;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eCK MB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eBrain Natriuretic Peptide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e508\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eNerve Conduction Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eNormal (MNCS and SNCS)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eElectromyography\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eMyogenic pattern\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImaging\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e2D ECHO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eGlobal hypokinesia, Ejection Fraction \u0026ndash; 40%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eUltrasound whole abdomen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eBilateral moderate pleural effusion and moderate ascitis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eB/L Renal artery Doppler\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eWithin normal limits\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eMRI Thigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eThe obturator, gluteal, vastus, adductor, Sartorius, and graceless muscle groups appear spared.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Polyglucosan Body Myopathy, PGBM, Polyglucosan Bodies, Glycogen Storage Disorder, Muscle Weakness, Myopathy, Genetic Analysis, Histopathology, Differential Diagnosis, Muscle Disorders","lastPublishedDoi":"10.21203/rs.3.rs-8775190/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8775190/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePolyglucosan Body Myopathy Type 1 (PGBM1) is a rare autosomal recessive neuromuscular disorder caused by pathogenic variants in the RBCK1 gene. It is typically characterized by progressive myopathy, cardiomyopathy, and variable immune dysfunction. However, phenotypic variability, especially in the absence of immune abnormalities, has been increasingly recognized. This study aims to describe a pediatric case of PGBM1 with distinctive clinical features and no evidence of immune dysfunction.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA 17-year-old female, born to consanguineous parents (third-degree consanguinity), underwent detailed clinical, neurological, and genetic evaluation. The patient developed symptoms at eight years of age, and next-generation sequencing (NGS) were performed to confirm the molecular diagnosis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe patient exhibited progressive proximal limb and truncal weakness, bilateral ptosis, scapular winging, facial weakness, secondary amenorrhea, and cardiomyopathy, without any clinical or laboratory evidence of immune dysfunction. Genetic analysis revealed pathogenic variants in the RBCK1 gene, confirming the diagnosis of PGBM1. Notably, the absence of immune abnormalities contrasts with previously reported cases, emphasizing the phenotypic heterogeneity of PGBM1, even among individuals with similar genetic backgrounds.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis case expands the known phenotypic spectrum of PGBM1 and highlights the diagnostic complexity due to its variable clinical manifestations in pediatric patients. Early implementation of molecular genetic testing alongside a multidisciplinary clinical evaluation is crucial for accurate diagnosis, management, and genetic counseling. Ongoing documentation of such cases will enhance understanding of genotype\u0026ndash;phenotype correlations in this rare neuromuscular disorder.\u003c/p\u003e","manuscriptTitle":"Clinical, Neurological, and Genetic Characterization of Polyglucosan Body Myopathy Type 1 (PGBM1) in a Pediatrics Patient: Expanding the Spectrum of RBCK1-Related Disorders","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-27 11:25:10","doi":"10.21203/rs.3.rs-8775190/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c7299d34-05db-480b-aee0-e81bcc528364","owner":[],"postedDate":"February 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-07T10:57:27+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-27 11:25:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8775190","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8775190","identity":"rs-8775190","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}