Joubert syndrome combined with multiple hereditary diseases: a case report

Joubert syndrome combined with multiple hereditary diseases: a case report | 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 Case Report Joubert syndrome combined with multiple hereditary diseases: a case report Yongxin Liao, Xiaotong Pang, Yue Fang, Zhao Chen, Kun Dong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7306250/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 Joubert syndrome (JS) is a rare autosomal recessive ciliopathy that often overlaps clinically and genetically with other ciliopathies such as nephronophthisis (NPHP), Senior–Løken syndrome (SLSN), and Bardet–Biedl syndrome (BBS). Patients frequently progress to end-stage renal disease (ESRD), but data on kidney transplantation outcomes in individuals with multiple ciliopathy phenotypes remain limited. Case presentation We report a 14-year-old male with developmental delay, insulin-dependent diabetes, anemia, and ESRD, carrying a homozygous NPHP1 deletion and a heterozygous IFT172 nonsense variant. He also had clinical features consistent with JS, BBS, SLSN, and coexisting α-thalassemia. Following cadaveric kidney transplantation and a tacrolimus/mycophenolate-based regimen, the patient demonstrated marked improvements in renal function, growth, hemoglobin level, neurological status, and daily living ability (Barthel index 80→95). Glycemic control required insulin adjustment, while anemia was managed with erythropoietin and iron supplementation. Conclusion This case highlights the efficacy of kidney transplantation in complex ciliopathy phenotypes and expands the phenotypic spectrum associated with combined NPHP1 deletion and IFT172 variants. Multidisciplinary long-term care, tailored immunosuppressive strategies, and genetic counseling are essential for optimizing outcomes in such rare multisystem disorders. Joubert syndrome Bardet-Biedl syndrome kidney transplantation ciliopathy thalassemia Figures Figure 1 Background Joubert syndrome (JS) is a rare autosomal recessive disorder characterized by hypotonia, ataxia, developmental delay, abnormal respiratory patterns, and the pathognomonic “molar tooth sign” on brain imaging. It belongs to the spectrum of ciliopathies—disorders caused by defects in primary cilia structure or function. Ciliopathies frequently present with overlapping features, including renal, ocular, skeletal, and metabolic abnormalities.Nephronophthisis (NPHP), the most common genetic cause of childhood ESRD, results from mutations in more than 20 genes, most notably NPHP1. Patients typically show progressive tubulointerstitial fibrosis and cyst formation, often with extra-renal involvement. SLSN, caused by variants in NPHP-related genes, combines NPHP with retinal degeneration. Bardet–Biedl syndrome (BBS) is another ciliopathy marked by retinal dystrophy, obesity, polydactyly, and variable renal involvement. All four diseases are ciliopathies, and there is no radical cure, mainly relying on symptomatic supportive treatment[ 1 – 4 ]. Southeast Asian type α-thalassemia (--SEA/αα) is mostly mild and generally does not require intervention.Few reports have described kidney transplantation outcomes in patients with JS overlapping with other ciliopathies and hematologic disorders. Case presentation A 14-year-old male patient, 138 cm,28 kg (BMI 14.8) and blood type O+, presented oliguria, reduced tearing, limb weakness and inability to lift his head at 2 months old. At 6 months, he showed polydipsia, poor appetite and polyuria. At 2 years old, he developed global developmental delay, poor coordination and balance, clumsiness in fine and gross motor skills, cognitive impairment and hypoacusis. At 3 years old, abnormal blood glucose was detected, which was unresponsive to oral hypoglycemic drugs, requiring insulin therapy. At 8 years old, growth hormone deficiency was diagnosed; his height increased after treatment but was was discontinued at the family's request due to concerns about potential side effects. The etiology was not clarified timely due to insufficient family attention. He could understand simple instructions but struggled with complex situations and two-digit arithmetic, while daily communication was manageable. Physical examination revealed anemia, emaciation, chronic disease cachexia, ataxic gait, hypotonia, dental crowding, hearing impairment, nystagmus, amblyopia, delayed gross motor development and an indwelling peritoneal dialysis catheter. The patient's younger sister, father and mother had no manifestations of JS, with no similar cases in the family. High-throughput sequencing on July 26, 2023 showed homozygous deletion of exons 1–20 of NPHP1 gene and heterozygous variant of IFT172 gene c.4936C > T (p.Arg1646Ter). Peritoneal dialysis was initiated on October 11, 2023, followed by cadaveric left kidney transplantation on February 8, 2024. The donor was a 3-year-and-9-month-old male (weight 20 kg, height 104 cm, blood type O+) who died of traumatic brain injury. Long-term immunosuppressive regimen included tacrolimus combined with mycophenolate mofetil. One year post-transplantation, his height increased to 150 cm, weight to 35 kg, and BMI to 15.6. While his physical condition showed favorable prognosis after transplantation, choosing long-term home rehabilitation with exercises like running, basketball and table tennis to improve motor skills and coordination. Barthel index increased from 80 preoperatively to 95 postoperatively, with significantly reduced negative emotions. Renal function, growth and development, daily living abilities, social skills and hemoglobin were all improved. Postoperative glycemic control was poorer than preoperative. Before July 17, 2024, insulin lispro was administered (7 units in the morning, 5 at noon, 5 in the evening) without bedtime dose and oral hypoglycemics. Later, metformin was ineffective, so insulin lispro was increased to 9, 7 and 7 units respectively, maintaining normal blood glucose with improved glycosylated hemoglobinas,as illustrated in Fig. 1 b. From October 16 to November 16, 2024, recombinant human erythropoietin (3000 IU every other day) was given for one month, combined with oral ferrous gluconate, folic acid and vitamin B12; the same regimen was repeated from December 18, 2024 to January 18, 2025 and February 26 to March 26, 2025,as illustrated in Fig. 1 a. Due to thalassemia, his red blood cell count was normal but hemoglobin low. Approximately 250 days post-transplantation, red blood cell count increased compensatorily with concurrent hemoglobin rise; significant elevation of glomerular filtration rate was noted at around 350 days. Discussion JS, an autosomal recessive ciliopathy, genetic testing and clinical manifestations (cerebellar ataxia, hypotonia, mild intellectual disability, renal insufficiency) confirmed JS, likely the relatively mild type 4. Long-term rehabilitation post-transplant significantly improved neurological symptoms, consistent with Gagliardi’s findings[ 5 ], enhancing motor skills and Barthel Index by saving dialysis time for rehabilitation.NPHP, an autosomal recessive chronic kidney disease from over 20 gene mutations (e.g., NPHP1, NPHP3), causes tubulointerstitial fibrosis and progressive nephron loss. This case, conforming to the juvenile type (ESRD onset ~ 13 years), renal cysts and splenomegaly,as illustrated in Fig. 1 d. SLSN, from ciliary gene mutations (NPHP, RPGRIP1L, ollow TTC21B), typically involves retinitis pigmentosa[ 1 , 6 ]. The patient had only nystagmus and amblyopia without significant ophthalmoscopic abnormalities. The patient had diabetes since age 3, with genetic testing, dental crowding(as illustrated in Fig. 1 c), and multi-organ involvement confirming BBS. Post-transplant, hyperglycemia (potentially from tacrolimus or increased food intake) normalized with escalated insulin, restoring glycated hemoglobin. Notably, he remained underweight (unlike Devarajan’s case[ 7 ]), possibly due to impaired feeding autonomy, uremic gastrointestinal damage, or JS-related hypothalamic dysfunction. Post-transplant improvements in appetite, BMI, and nutrition markers were observed with a tacrolimus + mycophenolate mofetil regimen without long-term glucocorticoids. Metformin was discontinued due to BBS-related β-cell dysfunction from IFT172 mutation (metformin enhances peripheral sensitivity) and risks of renal burden/lactic acidosis[ 8 ]. Insulin lispro (9U pre-breakfast, 7U pre-lunch/dinner) achieved normoglycemia (fasting 3.9–6.1 mmol/L; random < 11.1 mmol/L). This notable case suggests that renal transplantation may be an effective intervention and may have efficacy in patients with complex ciliopathies. Long-term post-transplant rehabilitation was associated with modest improvements in functional status and mood. With increased insulin dosage, the patient achieved acceptable glycemic control. Post-transplant, slight increases in appetite, BMI, and nutrition-related markers were noted. Overall, this case highlights the need for further research into optimal multidisciplinary management, immunosuppressive, and rehabilitation strategies. Conclusion This is an adolescent with JS concurrent with SNLS, NPHP, BBS, and α-thalassemia suggests kidney transplantation’s efficacy in complex ciliopathies. Post-transplant, renal function, growth, daily living abilities (Barthel index 80→95), hemoglobin, and neurological symptoms improved with tacrolimus/mycophenolate, rehabilitation, adjusted insulin, and erythropoietin/iron. The superposition of NPHP1/IFT172 variants provides additional insights into the phenotypic diversity of ciliopathies, while also highlighting the importance of multidisciplinary care, long-term clinical monitoring, further exploration of optimal management strategies, and genetic counseling in the management of rare multi-system ciliopathies. The case report has limitations. Firstly, it involves only one patient, lacking sufficient case support, which restricts the generalizability of the conclusions and makes it difficult to widely apply to other patients with similar complex ciliopathy combinations. Secondly, the follow - up period after transplantation is relatively short, resulting in insufficient information on long - term outcomes such as the long - term stability of renal function and the long - term development of complications. Moreover, the association between NPHP1/IFT172 variant superposition and phenotypic diversity is only described at the case level, with an insufficient exploration of the underlying molecular mechanisms and genetic pathways. Declarations Acknowledgements We extend our gratitude to the patient and his family, along with the staff members of the Department of Organ Transplantation at Guangxi Medical University. Authors’ contributions LY and CZ were involved in the care of the patient. LY drafted the manuscript. PX and FY prepared the Figure 1 A-D.KD reviewed and edited the manuscript. Funding Guangxi Medical and Health Appropriate Technology Development and Promotion Project(S2024020). Data availability Data sharing is not applicable to this article as no datasets were generated or analyzed during the preparation of this case report. Ethical approval and consent to participate Not applicable. Consent for publication The patient’s parents have given written informed consent for publication of this case report and any accompanying images. Competing interests The authors declare no competing interests. References Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med. 2011;364(16):1533–43. Liu YX, Sun WY, Xue B, Zhang RK, Li WJ, Xie X, Fan ZC. ARL3 mediates BBSome ciliary turnover by promoting its outward movement across the transition zone. J Cell Biol 2022, 221(10). He K, Sun X, Chen C, Luc S, Robichaud JH, Zhang Y, Huang Y, Ji B, Ku PI, Subramanian R et al. Non-canonical CDK6 activity promotes cilia disassembly by suppressing axoneme polyglutamylation. J Cell Biol 2025, 224(2). Pooh RK, Takeda M, Itoh K, Yoshimatsu J, Ogo K, Machida M, Ohashi H, Shimokawa O. Open isthmus and lambda sign of early Joubert syndrome: elucidating development of molar tooth sign. Ultrasound Obstet Gynecol. 2024;64(6):836–40. Gagliardi C, Brenna V, Romaniello R, Arrigoni F, Tavano A, Romani M, Valente EM, Borgatti R. Cognitive rehabilitation in a child with Joubert Syndrome: Developmental trends and adaptive changes in a single case report. Res Dev Disabil. 2015;47:375–84. Hildebrandt F, Zhou W. Nephronophthisis-associated ciliopathies. J Am Soc Nephrol. 2007;18(6):1855–71. Devarajan P. Obesity and genitourinary anomalies in Bardet-Biedl syndrome after renal transplantation. Pediatr Nephrol. 1995;9(3):397–8. Zheng NX, Miao YT, Zhang X, Huang MZ, Jahangir M, Luo S, Lang B. Primary cilia-associated protein IFT172 in ciliopathies. Front Cell Dev Biol. 2023;11:1074880. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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1","display":"","copyAsset":false,"role":"figure","size":146061,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThis illustrates the improvement in renal function and anemia status following renal transplantation(a).This illustrates the improvement in glycosylated hemoglobin levels following renal transplantation(b).There is dental crowding(c). This illustrates the presence of renal cysts and splenomegaly in the patient(d).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7306250/v1/9d0638e1201f1008dcf60a4a.png"},{"id":97673981,"identity":"bc1f9aad-f4c0-4b98-af56-5995b84807fa","added_by":"auto","created_at":"2025-12-08 09:42:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":603410,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7306250/v1/1c290513-1b0b-4256-893e-5cc55d72f2c0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Joubert syndrome combined with multiple hereditary diseases: a case report","fulltext":[{"header":"Background","content":"\u003cp\u003eJoubert syndrome (JS) is a rare autosomal recessive disorder characterized by hypotonia, ataxia, developmental delay, abnormal respiratory patterns, and the pathognomonic \u0026ldquo;molar tooth sign\u0026rdquo; on brain imaging. It belongs to the spectrum of ciliopathies\u0026mdash;disorders caused by defects in primary cilia structure or function. Ciliopathies frequently present with overlapping features, including renal, ocular, skeletal, and metabolic abnormalities.Nephronophthisis (NPHP), the most common\u003c/p\u003e\u003cp\u003egenetic cause of childhood ESRD, results from mutations in more than 20 genes, most notably NPHP1. Patients typically show progressive tubulointerstitial fibrosis and cyst formation, often with extra-renal involvement. SLSN, caused by variants in NPHP-related genes, combines NPHP with retinal degeneration. Bardet\u0026ndash;Biedl syndrome (BBS) is another ciliopathy marked by retinal dystrophy, obesity, polydactyly, and variable renal involvement. All four diseases are ciliopathies, and there is no radical cure, mainly relying on symptomatic supportive treatment[\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Southeast Asian type α-thalassemia (--SEA/αα) is mostly mild and generally does not require intervention.Few reports have described kidney transplantation outcomes in patients with JS overlapping with other ciliopathies and hematologic disorders.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 14-year-old male patient, 138 cm,28 kg (BMI 14.8) and blood type O+, presented oliguria, reduced tearing, limb weakness and inability to lift his head at 2 months old. At 6 months, he showed polydipsia, poor appetite and polyuria. At 2 years old, he developed global developmental delay, poor coordination and balance, clumsiness in fine and gross motor skills, cognitive impairment and hypoacusis. At 3 years old, abnormal blood glucose was detected, which was unresponsive to oral hypoglycemic drugs, requiring insulin therapy. At 8 years old, growth hormone deficiency was diagnosed; his height increased after treatment but was was discontinued at the family's request due to concerns about potential side effects. The etiology was not clarified timely due to insufficient family attention. He could understand simple instructions but struggled with complex situations and two-digit arithmetic, while daily communication was manageable. Physical examination revealed anemia, emaciation, chronic disease cachexia, ataxic gait, hypotonia, dental crowding, hearing impairment, nystagmus, amblyopia, delayed gross motor development and an indwelling peritoneal dialysis catheter.\u003c/p\u003e\u003cp\u003eThe patient's younger sister, father and mother had no manifestations of JS, with no similar cases in the family. High-throughput sequencing on July 26, 2023 showed homozygous deletion of exons 1\u0026ndash;20 of NPHP1 gene and heterozygous variant of IFT172 gene c.4936C\u0026thinsp;\u0026gt;\u0026thinsp;T (p.Arg1646Ter). Peritoneal dialysis was initiated on October 11, 2023, followed by cadaveric left kidney transplantation on February 8, 2024. The donor was a 3-year-and-9-month-old male (weight 20 kg, height 104 cm, blood type O+) who died of traumatic brain injury. Long-term immunosuppressive regimen included tacrolimus combined with mycophenolate mofetil. One year post-transplantation, his height increased to 150 cm, weight to 35 kg, and BMI to 15.6.\u003c/p\u003e\u003cp\u003eWhile his physical condition showed favorable prognosis after transplantation, choosing long-term home rehabilitation with exercises like running, basketball and table tennis to improve motor skills and coordination. Barthel index increased from 80 preoperatively to 95 postoperatively, with significantly reduced negative emotions. Renal function, growth and development, daily living abilities, social skills and hemoglobin were all improved.\u003c/p\u003e\u003cp\u003ePostoperative glycemic control was poorer than preoperative. Before July 17, 2024, insulin lispro was administered (7 units in the morning, 5 at noon, 5 in the evening) without bedtime dose and oral hypoglycemics. Later, metformin was ineffective, so insulin lispro was increased to 9, 7 and 7 units respectively, maintaining normal blood glucose with improved glycosylated hemoglobinas,as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb.\u003c/p\u003e\u003cp\u003eFrom October 16 to November 16, 2024, recombinant human erythropoietin (3000 IU every other day) was given for one month, combined with oral ferrous gluconate, folic acid and vitamin B12; the same regimen was repeated from December 18, 2024 to January 18, 2025 and February 26 to March 26, 2025,as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea.\u003c/p\u003e\u003cp\u003eDue to thalassemia, his red blood cell count was normal but hemoglobin low. Approximately 250 days post-transplantation, red blood cell count increased compensatorily with concurrent hemoglobin rise; significant elevation of glomerular filtration rate was noted at around 350 days.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eJS, an autosomal recessive ciliopathy, genetic testing and clinical manifestations (cerebellar ataxia, hypotonia, mild intellectual disability, renal insufficiency) confirmed JS, likely the relatively mild type 4. Long-term rehabilitation post-transplant significantly improved neurological symptoms, consistent with Gagliardi\u0026rsquo;s findings[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], enhancing motor skills and Barthel Index by saving dialysis time for rehabilitation.NPHP, an autosomal recessive chronic kidney disease from over 20 gene mutations (e.g., NPHP1, NPHP3), causes tubulointerstitial fibrosis and progressive nephron loss. This case, conforming to the juvenile type (ESRD onset\u0026thinsp;~\u0026thinsp;13 years), renal cysts and splenomegaly,as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ed. SLSN, from ciliary gene mutations (NPHP, RPGRIP1L, ollow TTC21B), typically involves retinitis pigmentosa[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The patient had only nystagmus and amblyopia without significant ophthalmoscopic abnormalities.\u003c/p\u003e\u003cp\u003eThe patient had diabetes since age 3, with genetic testing, dental crowding(as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec), and multi-organ involvement confirming BBS. Post-transplant, hyperglycemia (potentially from tacrolimus or increased food intake) normalized with escalated insulin, restoring glycated hemoglobin. Notably, he remained underweight (unlike Devarajan\u0026rsquo;s case[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]), possibly due to impaired feeding autonomy, uremic gastrointestinal damage, or JS-related hypothalamic dysfunction. Post-transplant improvements in appetite, BMI, and nutrition markers were observed with a tacrolimus\u0026thinsp;+\u0026thinsp;mycophenolate mofetil regimen without long-term glucocorticoids.\u003c/p\u003e\u003cp\u003eMetformin was discontinued due to BBS-related β-cell dysfunction from IFT172 mutation (metformin enhances peripheral sensitivity) and risks of renal burden/lactic acidosis[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Insulin lispro (9U pre-breakfast, 7U pre-lunch/dinner) achieved normoglycemia (fasting 3.9\u0026ndash;6.1 mmol/L; random\u0026thinsp;\u0026lt;\u0026thinsp;11.1 mmol/L).\u003c/p\u003e\u003cp\u003eThis notable case suggests that renal transplantation may be an effective intervention and may have efficacy in patients with complex ciliopathies. Long-term post-transplant rehabilitation was associated with modest improvements in functional status and mood. With increased insulin dosage, the patient achieved acceptable glycemic control. Post-transplant, slight increases in appetite, BMI, and nutrition-related markers were noted. Overall, this case highlights the need for further research into optimal multidisciplinary management, immunosuppressive, and rehabilitation strategies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis is an adolescent with JS concurrent with SNLS, NPHP, BBS, and α-thalassemia suggests kidney transplantation\u0026rsquo;s efficacy in complex ciliopathies. Post-transplant, renal function, growth, daily living abilities (Barthel index 80\u0026rarr;95), hemoglobin, and neurological symptoms improved with tacrolimus/mycophenolate, rehabilitation, adjusted insulin, and erythropoietin/iron. The superposition of NPHP1/IFT172 variants provides additional insights into the phenotypic diversity of ciliopathies, while also highlighting the importance of multidisciplinary care, long-term clinical monitoring, further exploration of optimal management strategies, and genetic counseling in the management of rare multi-system ciliopathies.\u003c/p\u003e\u003cp\u003eThe case report has limitations. Firstly, it involves only one patient, lacking sufficient case support, which restricts the generalizability of the conclusions and makes it difficult to widely apply to other patients with similar complex ciliopathy combinations. Secondly, the follow - up period after transplantation is relatively short, resulting in insufficient information on long - term outcomes such as the long - term stability of renal function and the long - term development of complications. Moreover, the association between NPHP1/IFT172 variant superposition and phenotypic diversity is only described at the case level, with an insufficient exploration of the underlying molecular mechanisms and genetic pathways.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe extend our gratitude to the patient and his family, along with the staff members of the Department of Organ Transplantation at Guangxi Medical University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLY and CZ were involved in the care of the patient. LY drafted the manuscript. PX and FY prepared the Figure 1 A-D.KD reviewed and edited the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGuangxi Medical and Health Appropriate Technology Development and Promotion Project(S2024020).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analyzed during the preparation of this case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient\u0026rsquo;s parents have given written informed consent for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med. 2011;364(16):1533\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu YX, Sun WY, Xue B, Zhang RK, Li WJ, Xie X, Fan ZC. ARL3 mediates BBSome ciliary turnover by promoting its outward movement across the transition zone. J Cell Biol 2022, 221(10).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHe K, Sun X, Chen C, Luc S, Robichaud JH, Zhang Y, Huang Y, Ji B, Ku PI, Subramanian R et al. Non-canonical CDK6 activity promotes cilia disassembly by suppressing axoneme polyglutamylation. J Cell Biol 2025, 224(2).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePooh RK, Takeda M, Itoh K, Yoshimatsu J, Ogo K, Machida M, Ohashi H, Shimokawa O. Open isthmus and lambda sign of early Joubert syndrome: elucidating development of molar tooth sign. Ultrasound Obstet Gynecol. 2024;64(6):836\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGagliardi C, Brenna V, Romaniello R, Arrigoni F, Tavano A, Romani M, Valente EM, Borgatti R. Cognitive rehabilitation in a child with Joubert Syndrome: Developmental trends and adaptive changes in a single case report. Res Dev Disabil. 2015;47:375\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHildebrandt F, Zhou W. Nephronophthisis-associated ciliopathies. J Am Soc Nephrol. 2007;18(6):1855\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDevarajan P. Obesity and genitourinary anomalies in Bardet-Biedl syndrome after renal transplantation. Pediatr Nephrol. 1995;9(3):397\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZheng NX, Miao YT, Zhang X, Huang MZ, Jahangir M, Luo S, Lang B. Primary cilia-associated protein IFT172 in ciliopathies. Front Cell Dev Biol. 2023;11:1074880.\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"Joubert syndrome, Bardet-Biedl syndrome, kidney transplantation, ciliopathy, thalassemia","lastPublishedDoi":"10.21203/rs.3.rs-7306250/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7306250/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eJoubert syndrome (JS) is a rare autosomal recessive ciliopathy that often overlaps clinically and genetically with other ciliopathies such as nephronophthisis (NPHP), Senior–Løken syndrome (SLSN), and Bardet–Biedl syndrome (BBS). Patients frequently progress to end-stage renal disease (ESRD), but data on kidney transplantation outcomes in individuals with multiple ciliopathy phenotypes remain limited.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation \u003c/strong\u003eWe report a 14-year-old male with developmental delay, insulin-dependent diabetes, anemia, and ESRD, carrying a homozygous NPHP1 deletion and a heterozygous IFT172 nonsense variant. He also had clinical features consistent with JS, BBS, SLSN, and coexisting α-thalassemia. Following cadaveric kidney transplantation and a tacrolimus/mycophenolate-based regimen, the patient demonstrated marked improvements in renal function, growth, hemoglobin level, neurological status, and daily living ability (Barthel index 80→95). Glycemic control required insulin adjustment, while anemia was managed with erythropoietin and iron supplementation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion \u003c/strong\u003eThis case highlights the efficacy of kidney transplantation in complex ciliopathy phenotypes and expands the phenotypic spectrum associated with combined NPHP1 deletion and IFT172 variants. Multidisciplinary long-term care, tailored immunosuppressive strategies, and genetic counseling are essential for optimizing outcomes in such rare multisystem disorders.\u003c/p\u003e","manuscriptTitle":"Joubert syndrome combined with multiple hereditary diseases: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-30 07:20:41","doi":"10.21203/rs.3.rs-7306250/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":"297406ea-654a-41e2-9baa-1eb72caf308c","owner":[],"postedDate":"September 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-08T08:24:31+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-30 07:20:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7306250","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7306250","identity":"rs-7306250","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}