Novel Mutations of the SPI1 Gene in a Chinese Girl with Agammaglobulinemia

Novel Mutations of the SPI1 Gene in a Chinese Girl with Agammaglobulinemia | 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 Novel Mutations of the SPI1 Gene in a Chinese Girl with Agammaglobulinemia Ping Wu, Jing Zhao, Zilong Yu, Hongwei Li, Zhenwei Liu, Yinghui Peng, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7538129/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Mar, 2026 Read the published version in BMC Pediatrics → Version 1 posted 17 You are reading this latest preprint version Abstract Background: Agammaglobulinemia is a rare immune disorder characterized by deficient immunoglobulin production, primarily affecting the B cells of the immune system. Case Report: A 13-year-old girl was admitted to the hospital due to "recurrent respiratory infections for over 6 years, accompanied by cough and fever for more than 1 week". She had experienced recurrent fever, cough, and purulent sputum approximately once every 2 months. Investigation: Immunoglobulin testing revealed significantly decreased IgG and IgA levels, with both the ratio of B lymphocytes (CD3 - CD19 + )/ lymphocytes and the absolute B cell count being 0, leading to a preliminary diagnosis of immune deficiency. Genetic testing was performed on the patient, her younger brother and their parents to determine the specific type of immune deficiency. Results showed that the patient carried a heterozygous mutation in the SPI1 gene (c.566T>C, p.Ile189Thr), confirming a diagnosis of autosomal dominant agammaglobulinemia. This mutation was inherited from her mother; neither her father nor her younger brother carried it. A literature review indicated that the c.566T>C mutation in the SPI1 gene had not been previously reported. Additionally, we summarized the clinical and genetic characteristics of patients from different continents. The patient received anti-infection treatment with piperacillin-tazobactam and voriconazole, intravenous gamma globulin infusion, bronchoscopic lavage, and symptomatic treatment (e.g., antipyretic, antitussive, expectorant, and nutritional support). Her condition improved rapidly, and she was discharged. Long-term follow-up showed that she received monthly intravenous gamma globulin infusions at a local hospital. Conclusion: This study reports a case of autosomal dominant agammaglobulinemia caused by a novel SPI1 gene mutation. To date, this mutation has not been recorded in Chinese reference gene databases or the global Genome Aggregation Database (gnomAD). Our findings suggest that whole-exome sequencing for detecting such mutations could improve the identification and early diagnosis of agammaglobulinemia, particularly in homozygous individuals with SPI1 mutations. These SPI1 mutations may represent a novel therapeutic target for the agammaglobulinemia in the future. Novel mutations SPI1 gene Agammaglobulinemia Figures Figure 1 Figure 2 Introduction Agammaglobulinemia, as a primary immunodeficiency disease, is mainly characterized by a severe reduction or absence of B lymphocytes in peripheral blood, which in turn leads to low or near deficiency of serum immunoglobulin levels[ 1 – 2 ]. Clinically, patients usually present with recurrent rhinosinusitis and pulmonary infections[ 3 – 4 ]. In severe cases, systemic infections may occur, posing a serious threat to health and survival[ 5 ]. X-linked agammaglobulinemia (XLA) is one of the most common primary immunodeficiency disorders in children, exhibiting X-linked recessive inheritance, with most patients being male[ 6 – 8 ]. Beyond XLA, autosomal dominant and recessive forms of agammaglobulinemia also exist[ 9 – 10 ]; these are rarer, with fewer associated studies. This report describes a case of autosomal dominant angammaglobulinemia caused by a SPI1 gene mutation, enriching the genotypic spectrum of angammaglobulinemia and providing new data for research on this disease. Through detailed analysis of this case, we aim to deepen understanding of autosomal dominant angammaglobulinemia and offer valuable references for clinical diagnosis and treatment. Clinical Information A 13-year-old girl was admitted due to cough and fever lasting over 1 week. She had experienced recurrent lower respiratory tract infections since the age of 2, approximately once every 2 months. Two months prior, she was treated in the pediatric intensive care unit (PICU) for severe pneumonia lasting 1 month. She was born to prematurely via natural delivery at 34 weeks of gestation, with a birth weight of 2.6 kg. Her parents were healthy, non-consanguineous, and denied any family history of genetic diseases. Physical examination revealed coarse breath sounds in both lungs, with scattered fine moist rales. Her growth and development were normal. Laboratory tests showed significantly elevated infammatory markers (Table 1 ), decreased total protein and albumin(Table 2 ), markedly reduced IgG and IgA, and a B lymphocyte ratio (CD3 − CD19 + )/ lymphocytes and absolute B cell count of 0 (Table 3 ). Cytokine profiles are shown in Table 4 , supporting a preliminary diagnosis of immune deficiency. Genetic testing of the patient, her younger brother, and parents revealed heterozygous mutations c.566T > C and p.Ile189Thr in the patient’s SPI1 gene (Fig. 1 A). Further analysis confirmed that the mutation was inherited from her mother; neither her father nor brother carried it (Fig. 1 B-C). Paranasal sinus CT scans showed inflammation in both maxillary sinuses, ethmoid sinuses and the right frontal sinus (Fig. 1 D-F). Chest CT scans revealed extensive bilateral pulmonary inflammation, with inflammatory nodules in the apical posterior segment of the left upper lung and the extrapulmonary basal segment of the left lower lung (Fig. 2 A-C). Bronchoscopy detected copious sputum in multiple lung lobes, including the tracheal carina, left main bronchus, left lower lobe, and bronchus intermedius (Fig. 2 D). Table 1 Clinical characteristics of blood diagnostics ( n = 6), median (IQR) Parameters Measured values Normal range Absolute number of white blood cell, median (IQR), 10 9 /L 12.58 (5-30.36) a 3.5–9.5 Absolute number of neutrophil, median (IQR), 10 9 /L 9.2(3.02–26.7) a 1.8–6.3 Percentage of neutrophil, median (IQR), % 65.74 (43.7–87.9) 40–75 Absolute number of lymphocytes, median (IQR), 10 9 /L 2.42 (1.39–3.5) 1.1–3.2 Percentage of lymphocytes, median (IQR), % 24.68 (7.4–42.6) 20–50 Absolute number of monocytes, median (IQR), 10 9 /L 0.81(0.39–1.3) a 0.1–0.6 Percentage of monocyte, median (IQR), % 7.83(4.3–10.7) 3.0–10.0 Absolute number of red blood cell, median (IQR), 10 12 /L 4.84 (4.38–5.13) 3.8–5.1 Hemoglobin, median (IQR), g/l 122.33 (114–132) 115–150 Hematocrit, median (IQR), % 38.2 (34–41) 35–45 Mean hemoglobin amount, median (IQR), pg 25.25 (24-25.7) b 27–34 Mean hemoglobin concentration, median (IQR), g/l 324.83 (319–340) 316–354 Platelet, median (IQR), 10 9 /L 249.33(168–312) 126–350 Platelet distribution width, median (IQR), % 42.04(35.5-48.13) a 9.0–17.0 C-reactive protein, median (IQR), mg/L 3.04(0.72–7.4) a 0-0.6 The table shows the statistically significant differences between measurement results and normal range (p < 0.05). a The values higher than normal range. b The values are lower than normal range. Table 2 Clinical characteristics of biochemical detection indices ( n = 4), median (IQR) Parameters Measured values Normal range Aspartate amino transferase, median (IQR), U/L 17.43(11.7–24.5) 13–35 Creatine kinase, median (IQR), U/L 45.6(40-51.3) 40–200 Creatine kinase isoenzyme, median (IQR), U/L 17(15–20) 3.0–25 Lactate dehydrogenase, median (IQR), U/L 174.67(131–236) 120–250 High-sensitivity troponinⅠ, median (IQR), pg/mL 3.7(2-4.7) 0-17.5 Myohemoglobin, median (IQR), ug/L 6.13(5.7-7) <70 Alkaline phosphatase, median (IQR), U/L 143.4 81–454 Alanine aminotransferase, median (IQR), U/L 13.1(5.8–26.9) 7–40 Total protein, median (IQR), g/L 59.6(56.7–63.6) b 65–85 Albumin, median (IQR), g/L 39.38 (35.8–42.2) b 40–55 Natrium, median (IQR), mmol/L 140.6(139.8–142) 135–145 Kalium, median (IQR), mmol/L 3.74(3.35–4.09) 3.5-5.0 Chlorinum, median (IQR), mmol/L 106.27(105.1–109) 99–110 Calcium, median (IQR), mmol/L 2.27 (2.18–2.35) 2.24–2.74 Creatinine, median (IQR), µmol/L 41.17(37.8–47.6) 33–75 The table shows the statistically significant differences between measurement results and normal range (p < 0.05). a The values higher than normal range. b The values are lower than normal range. Table 3 Clinical characteristics of immune-related indices ( n = 5), median (IQR). Parameters Measured values Normal range IgG, g/L 3.94(2.89–5.09) b 7.0–16.0 IgA, g/L 0(0-0.01) b 0.7-5.0 IgM, g/L 0.57(0.15–0.67) 0.4–2.8 C3, g/L 1.15(1.05–1.33) 0.9–1.8 C4, g/L 0.28(0.28–0.32) b 0.1–0.4 B cells/lymphocytes (CD19+), % 0.03 (0-0.1) b 5–18 Absolute count of B cells (CD19 + Abs), cells/uL 1(0–3) b 90–560 T cells/lymphocytes (CD3+/CD45+), % 84.3 (81.3–90.5) a 50–84 Absolute count of T cells (CD3 + Abs), cells/uL 2231 (1361–2729) 955–2860 Helper T cells/lymphocytes (CD3+/CD4+), % 22.86(18.7–25.7) b 30–60 Absolute count of helper T cells (CD3+/CD4 + Abs), cells/uL 686.67(411–832) 550–1440 Inhibit T cells/lymphocytes (CD3+/CD8+), % 50.96(46.4–65.1) a 13–41 Absolute count of inhibit T cells (CD3+/CD8 + Abs), cells/uL 1265.33(775–1550) a 320–1250 NK cells/lymphocytes (CD16+/CD56+), % 16.27(14.5–17.6) 7–40 Absolute count of NK cells (NK Abs), cells/uL 447.33(234–560) 150–1100 The table shows the statistically significant differences between measurement results and normal range (p < 0.05). The measurement results with red color are the values higher than normal range. The blue ones are lower than normal range. The black ones are in the normal range. Table 4 Clinical characteristics of cytokines ( n = 3), median (IQR). Parameters Measured values Normal range IL-5, pg/mL 0.77(0.36–1.43) 0-3.1 IL-17A, pg/mL 1.74 (0.63–2.38) 0-20.6 IL-1β, pg/mL 2.42 (0.82–4.08) 0-12.4 IL-2, pg/mL 1.08 (0.79–1.34) 0-5.71 IL-4, pg/mL 0.90 (0.58–1.21) 0-2.8 IL-6, pg/mL 384.81 (12.45-1126.9) a 0-5.3 IL-8, pg/mL 508.56 (9.44-1238.7) a 0-20.6 IL-10, pg/mL 18.20 (1.52–49.11) a 0-4.91 IL-12p70, pg/mL 1.64 (0.68–2.18) 0-3.4 TNF-α, pg/mL 1.23 (0.37–1.72) 0-4.6 TNF-β, pg/mL 1.71(0.75–2.19) 0-7.42 IFN-γ, pg/mL 2.5 (2.11–2.92) 0-4.6 The table shows the statistically significant differences between measured values and normal range (p < 0.05). Treatment results and prognosis Following active anti-infection therapy, intravenous gamma globulin infusion, bronchoscopic lavage, and supportive care, the patient's condition improved gradually. Her body temperature normalized, and after over 72 hours, cough and expectoration significantly diminished. Pulmonary nodules resolved, and inflammatory markers(e.g., white blood cell count and C-reactive protein) returned to normal ranges. Follow-up chest and paranasal sinus CT scans showed marked absorption of pulmonary inflammation, reduced inflammatory nodules and lung abcess, and alleviated paranasal sinus inflammation. The patient’s mental status snd appetite improved, with stable vital signs, meeting discharge criteria. After discharge, she received intravenous gamma globulin (6g) every 4 weeks. During follow-up, no severe infections (e.g., sepsis, meningitis) occurred, and her growth and development gradually normalized. Literature review We searched PubMed using the keywords “agammaglobulinemia”, “X-linked”, “autosomal dominant”, and “autosomal recessive”, reviewing English and Chinese literature from 1965 to 2025. Studies identifying associated genes were included, and differences among patients from various continents were analyzed (Table 5 and Supplemental Table 4). Table 5 Autosomal genetic characteristics of agammaglobulinemia patients across different countries. Country China[ 11 – 15 ] Switzerland[ 16 ] United Kingdom[ 17 ] Republic of Serbia[ 18 ] Japan[ 19 ] Australia[ 20 ] USA[ 21 ] Autosomal Dominant heterozygous mutationof TCF3 gene : c.1663G > A(p.E555K); mutation of the STAT1 gene : c.1154 C > T; c.821G > A(p.R274Q); heterozygous mutationof NFKB2 gene : c.2540dupT mutation of the PIK3CD gene : c.3061G>A(E1021K); c.3061G>A; monoallelic LIG4 missense mutations : c.G1739A mutation of the CTLA4 gene : c.105C > A(p.035*); c.110 + 1G > T; c.208C > T(p.R70W); c.371A > C(p.T124P); с.223C > T(p.R75W); c. 2T > C; mutation of the SPI1 gene : c.441dup; mutation of the TCF3 gene : c.1663G > A(p.E555K); mutation of the NFKB2 gene : c.2594A > G; heterozygous mutationof SPI1 gene : c.325_327delGGCinsAG(p.G109Sfs*78); c.331C > T(p.Q111X); c.366C > A(p.Y122X); c.635A > C(p.H212P); c.696_697delGC(p.L233Afs*53); c.725T > G(p.V242G); Country Sharjah [ 22 ] Iran [ 23 ] China [ 24 , 25 ] Argentinia [ 26 ] USA [ 26 , 27 ] Sweden [ 26 ] Span [ 26 ] Italy [ 26 ] Autosomal Recessive mutation of the PIK3R1 gene : c.244dup(p.(lle82Asnfs*24)chr5: 67522740) mutation of the IGLL1 gene : c.258delG mutation of the µHC gene : c.1956G > A; heterozygous mutationof DNMT38 gene : c.2477G > A(p.R826H) mutation of the IGHM gene : c.258G>A mutation of the IGHM gene : c.433G>A; c.412T>G; Defects in the mu heavy-chain gene : c.1768T>G mutation of the IGHM gene : c.433G>A; mutation of the IGHM gene : c.168AAdel; c.433G>A; mutation of the IGHM gene : c.433G>A; Discussion In rare disease research, agammaglobulinemia-a primary immunodeficiency disorder- has long been a focus of global scholars. XLA, with its relatively high incidence and clear genetic mechanism, has been extensively studied[ 28 ]. Since Bruton first reported XLA in 1952, numerous studies have been conducted worldwide[ 29 ]. XLA is caused by mutations in the gene encoding Bruton's tyrosine kinase (BTK) on the X chromosome, disrupting B cell differentiation and maturation[ 30 ]. Most patients are male, presenting with recurrent bacterial infections, significantly reduced or absent serum immunoglobulins, and decreased circulating B lymphocytes[ 31 – 32 ]. BTK mutations are detectable in 80% − 90% of clinically diagnosed cases[ 33 – 34 ], including single-nucleotide deletions, substitutions, insertions, frameshift, nonsense, and missense mutations[ 35 – 36 ]. In contrast, research on autosomal dominant or recessive agammaglobulinemia began later. Due to rarity, such studies are challenging but have made progress in recent years. Through studies of agammaglobulinemia patients, international scholars have identified multiple autosomal recessive mutations, including those in µHC, PIK3R1, TCF3, and SLC39A7[ 37 – 40 ]. These mutations impair genes regulating early B cell differentiation and function, triggering agammaglobulinemia. Patients with autosomal recessive agammaglobulinemia (ARA) exhibit earlier onset and higher susceptibility to severe complications[ 41 – 42 ]. Regarding SPI1 mutations and agammaglobulinemia, researchers at Children's Hospital of Philadelphia performec exome sequencing on 30 global patients with absent B lymphocytes, finding SPI1 mutations in 6 cases[ 43 ]. SPI1 encodes the PU.1 protein, which plays a critical role in B lymphocyte development by facilitating chromatin accessibility in bone marrow B cells[ 44 ]. PU.1 deficiency blocks this accessibility, preventing B cell formation and causing agammaglobulinemia[ 45 ]. In vitro CRISPR-based studies confirmed the roles of SPI1 and PU.1, revealing B cells’ high sensitivity to PU.1 perturbations[ 46 – 47 ]. Despite progress, many aspects of agammaglobulinemia remain unclear, particularly the molecular mechanisms by which SPI1 mutations cause the disease and the development of more effective treatments, requiring further research. This study employed multiple methods to ensure scientific rigor: detailed recording and analysis of the patient’s medical history, clinical manifestations, laboratory results, and genetic data to clarify desease progression, providing direct clinical evidence; and comprehensive review of domestic and international literature to contextualize research status and progress, offering theoretical support. The key innovation lies in identifying a novel autosomal dominant agammaglobulinemia mutation: whole-exome sequencing revealed heterozygous SPI1 mutations (c.566T > C, p.Ile189Thr), unreported previously, enriching the disease’s genotypic spectrum. Additionally, this case highlights the possibility of congenital agammaglobulinemia in females. While X-linked agammaglobulinemia predominantly affects males, this female patient-carrying a maternally inherited mutation—demonstrates that autosomal dominant inheritance can affect females, broadening understanding of the disease’s genetic characteristics. This single-case study provides new insights and data for autosomal dominant agammaglobulinemia research but has limitations. The small sample size may introduce bias, failing to represent the full spectrum of autosomal dominant agammaglobulinemia. Limitations exist in analyzing incidence, clinical diversity, and treatment responses, hindering in-depth statistical analysis. Future research should collect more cases via multi-center collaboration to establish large cohorts, enabling comprehensive characterization of clinical features, genetics, and therapeutic efficacy. Large-scale studies could reveal disease patterns, risk factors, and treatment safety/effectiveness, strengthening clinical evidence. With advancing genetic testing, whole-exome sequencing is widely used in rare disease diagnosis. Future studies should enhance genetic testing for undiagnosed agammaglobulinemia patients to identify new pathogenic genes and mutations, investigate their mechanisms, and improve diagnostic accuracy. Exploring novel therapies—such as gene editing to repair/replace mutated genes—could offer curative potential, though challenges (e.g., precision, safety, ethics) in clinical application require resolution. Optimizing stem cell transplantation protocols to increase success rates and reduce complications may also expand treatment options. Future research should also address quality of life and mental health in agammaglobulinemia patients. Long-term treatment and life restrictions may induce anxiety or depression; studies should explore psychological support and social care strategies to improve quality of life, and optimize treatments to minimize disruption, facilitating social integration. Abbreviations gnomAD: Genome Aggregation Database; XLA: X-linked agammaglobulinemia; PICU: pediatric intensive care unit; BTK: Bruton's tyrosine kinase; ARA: Autosomal recessive agammaglobulinemia. Declarations Acknowledgments We thank the family of the reported individual, Guangzhou Amcare Genomic Laboratory and colleagues from the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China. Authors’ contributions All authors contributed and critically revised the manuscript. PW, DHC and CYL conceptualized the idea; PW, JZ and ZC drafted the manuscript and revised the manuscript; ZLY, HWL, ZWL and YHP collected the data. All authors approved of the final manuscript. Funding This work was supported by the Western Medicine-General Guide Item of Guangzhou Municipal Health Commission (No. 20241A011039). Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate This study was approved by the ethical committees of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China. Written informed consent of this study was obtained from his parents of this patient. Consent for publication Written informed consent of this case report obtained from his parents of this patient was approved for publication. Competing interests The authors declare that they have no competing interests. Author details 1 Department of Pediatrics, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, Guangdong, China. 2 Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China. 3 Department of Allergy, Immunology and Rheumatology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China. References Khoshnevisan, R, Hassanzadeh, S, Klein, C, et al. B-cells absence in patients diagnosed as inborn errors of immunity: a registry-based study. IMMUNOGENETICS. 2024; 76 (3): 189-202. doi: 10.1007/s00251-024-01342-y Markocsy, A, Kapustová, D, Čereš, A, et al. Atypical Manifestation of X-linked Agammaglobulinemia - the Importance of Genetic Testing. Acta Medica (Hradec Kralove). 2024; 67 (2): 60-63. doi: 10.14712/18059694.2024.21 Karadeniz, EB, Aliyeva, C, Aydemir, S, et al. Chronic Rhinosinusitis in Patients with Primary Immunodeficiency. INT ARCH ALLERGY IMM. 2022; 184 (3): 302-310. doi: 10.1159/000527265 Ivankovich‐Escoto, G, Danielian, S, Morera, E, et al. Clinical, immunological and genetic characterization of patients with X‐linked agammaglobulinemia in Costa Rica SCAND J IMMUNOL. 2022; 97 (1): doi: 10.1111/sji.13237 Thangaraj, A, Sil, A, Goel, S, et al. Disseminated Aspergillosis in X-linked Agammaglobulinemia: Beyond the norm. J CLIN IMMUNOL. 2024; 45 (1): 24. doi: 10.1007/s10875-024-01815-5 Madathil Govindaraj, G, Jain, A, Edavazhippurath, A, et al. Clinical, immunological and genomic characteristics of children with X-linked agammaglobulinemia from Kerala, South India. HUM IMMUNOL. 2022; 83 (4): 335-345. doi: 10.1016/j.humimm.2022.01.003 Cardenas-Cruz, C, Jiménez-Santana, L, Campos-Lopez, D, et al. X-linked agammaglobulinemia: 35 years of experience in a tertiary pediatric hospital in Latin America Int J Contemp Pediatrics. 2022; doi: 10.18203/2349-3291.ijcp20223151 Altman, K, Zhou, C, Hernandez-Trujillo, V, et al. Health-Related Quality of Life in 91 Patients with X-Linked Agammaglobulinemia. J CLIN IMMUNOL. 2022; 42 (4): 811-818. doi: 10.1007/s10875-022-01222-8 Patel, S, Roberts, R. Transient Hypogammaglobulinemia of Infancy, a Possible Autosomal Dominant Inheritance Pattern in Certain Families J ALLERGY CLIN IMMUN. 2006; 117 (2): S172. doi: 10.1016/j.jaci.2005.12.685 Cardenas-Morales, M, Hernandez-Trujillo, VP. Agammaglobulinemia: from X-linked to Autosomal Forms of Disease. CLIN REV ALLERG IMMU. 2021; 63 (1): 22-35. doi: 10.1007/s12016-021-08870-5 Xu Yingyang et al., A case of autosomal dominant agammaglobulinemia. Chinese Journal of Clinical Immunity and Allergy, 2021. 15(3): p.322-324. Chen Lanqin et al., Two Chinese cases with STAT1 gene gain-of-function variation. Chinese Journal of Pediatrics, 2021. 59(8): p.700-702. Wang Caihong et al., Two cases of congenital immunodeficiency with disseminated infection of cyanobacteria marneffei and literature review. Chinese Journal of Pediatric Emergency Medicine, 2020. 27(11): p.861-864. ZHENG Jing, XIAO Yangyang, LIU Liqun, et al. Activated PI3K-δ syndrome caused by PIK3CD gene mutation: a case report and literature review[J]. Journal of Clinical Pediatrics, 2019, 37(4): p. 301-303. Wang Jialan, PIK3CD gene mutation induced PI3Kδ hyperactivation syndrome in children: a report of 2 cases and literature review Abstract, 2022, Qingdao University. Jauch, A.J., et al., Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency. J Allergy Clin Immunol, 2023. 152(2): p. 500-516. Schubert, D., et al., Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med, 2014. 20(12): p. 1410-1416. Miskovic, R., et al., Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia. Front Immunol, 2024. 15: p. 1324679. Utsumi, T., et al., Exclusive Characteristics of the p.E555K Dominant-Negative Variant in Autosomal Dominant E47 Deficiency. J Clin Immunol, 2024. 44(7): p. 167. Lee, C.E., et al., Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. Blood, 2014. 124(19): p. 2964-72. Le Coz, C., et al., Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients. J Exp Med, 2021. 218(7). Syed, I.J., et al., A Novel Variant of the PIK3R1 Gene Mutation Associated With SHORT Syndrome and Agammaglobulinemia. Cureus, 2024. 16(6): p. e62983. Naiboglu, S., et al., Single Mutation Different Clinical Findings: IGLL1 Defect. Iran J Allergy Asthma Immunol, 2024. 23(4): p. 452-456. Zhang Zhiyong et al., Analysis of mutation in heavy chain-μ (μHC) gene in a Chinese patient with congenital agammaglobulinemia. Chinese Journal of Pediatrics, 2010. 48(4): p.279-283. Hu, S.C., et al., [Clinical and genetic manifestations of immunodeficiency, centromeric instability, and facial anomalies syndrome: a case report and literature review]. Zhonghua Er Ke Za Zhi, 2019. 57(1): p. 55-59. Lopez, G.E., et al., Clinical and molecular analysis of patients with defects in micro heavy chain gene. J Clin Invest, 2002. 110(7): p. 1029-35. Yel, L., et al., Mutations in the mu heavy-chain gene in patients with agammaglobulinemia. N Engl J Med, 1996. 335(20): p. 1486-93. Teocchi, M, de Andrade Eugênio, T, Furlaneto Marega, L, et al. Dysregulation of Toll-Like Receptor Signaling-Associated Gene Expression in X-Linked Agammaglobulinemia: Implications for Correlations Genotype-Phenotype and Disease Expression. J INNATE IMMUN. 2024; 16 (1): 425-439. doi: 10.1159/000540082 Conley, ME, Mathias, D, Treadaway, J, et al. Mutations in btk in patients with presumed X-linked agammaglobulinemia. AM J HUM GENET. 1998; 62 (5): 1034-43. doi: 10.1086/301828 Yang, YD, Tang, H, Li, W, et al. Identification by whole-exome sequencing of novel mutation c.64C > G in the BTK gene of a fetus with X-linked agammaglobulinemia. ULTRASOUND OBST GYN. 2015; 45 (6): 753-4. doi: 10.1002/uog.14738 Almutairy, KA, Alasmari, BG, Rayees, S. Digenic Inheritance of Hereditary Spherocytosis Type III and X-linked Agammaglobulinemia: Coexistence of Two Distinct Recessive Disorders in a Male Child. Cureus. 2024; 16 (9): e69887. doi: 10.7759/cureus.69887 Bagheri, Y, Vosughi, A, Azizi, G, et al. Comparison of clinical and immunological features and mortality in common variable immunodeficiency and agammaglobulinemia patients. IMMUNOL LETT. 2019; 210 55-62. doi: 10.1016/j.imlet.2019.05.001 Chung, M, Jung, J, Son, J, et al. A Case of X-Linked Agammaglobulinemia with Btk Gene Intron 2 Mutation TUBERC RESPIR DIS. 2008; 65 (3): 207. doi: 10.4046/trd.2008.65.3.207 Islam, TC, Smith, CI. The cellular phenotype conditions Btk for cell survival or apoptosis signaling. IMMUNOL REV. 2000; 178 49-63. doi: 10.1034/j.1600-065x.2000.17811.x Saha, BK, Curtis, SK, Vogler, LB, et al. Molecular and structural characterization of five novel mutations in the Bruton's tyrosine kinase gene from patients with X-linked agammaglobulinemia. MOL MED. 1997; 3 (7): 477-85. PMID: 9260159 Zaidi, SK, Qureshi, S, Qamar, FN. X-linked agammaglobulinemia - first case with Bruton tyrosine kinase mutation from Pakistan. J PAK MED ASSOC. 2017; 67 (3): 471-473. PMID: 28304004 Ferrari, S, Zuntini, R, Lougaris, V, et al. Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia. Genes Immun. 2007; 8 (4): 325-33. doi: 10.1038/sj.gene.6364391 Tang, P, Upton, JEM, Barton-Forbes, MA, et al. Autosomal Recessive Agammaglobulinemia Due to a Homozygous Mutation in PIK3R1. J CLIN IMMUNOL. 2017; 38 (1): 88-95. doi: 10.1007/s10875-017-0462-y Qureshi, S, Sheikh, MDA, Qamar, FN. Autosomal Recessive Agammaglobulinemia - first case with a novel TCF3 mutation from Pakistan. CLIN IMMUNOL. 2018; 198 100-101. doi: 10.1016/j.clim.2018.07.016 Erdős, M, Mironska, K, Kareva, L, et al. A novel mutation in SLC39A7 identified in a patient with autosomal recessive agammaglobulinemia: The impact of the J Project. PEDIAT ALLERG IMM-UK. 2022; 33 (6): e13805. doi: 10.1111/pai.13805 Shillitoe, B, Gennery, A. X-Linked Agammaglobulinaemia: Outcomes in the modern era. CLIN IMMUNOL. 2017; 183 54-62. doi: 10.1016/j.clim.2017.07.008 Rahmani, F, Aghamohammadi, A, Ochs, H, et al. Agammaglobulinemia: comorbidities and long-term therapeutic risks Expert Opin Orphan Drugs. 2017; 5 (7): 559-574. doi: 10.1080/21678707.2017.1330145 Le Coz, C, Nguyen, DN, Su, C, et al. Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients. J EXP MED. 2021; 218 (7): doi: 10.1084/jem.20201750 Wahlster, L, Sankaran, VG. I SPI1 something needed for B cells. J EXP MED. 2021; 218 (7): doi: 10.1084/jem.20210572 Miskovic, R, Ljubicic, J, Bonaci-Nikolic, B, et al. Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia. Front Immunol. 2024; 15 1324679. doi: 10.3389/fimmu.2024.1324679 Daddali, R, Kettunen, K, Turunen, T, et al. Novel heterozygous SPI1c.538C>T p.(Leu180Phe) variant causes PU.1 haploinsufficiency leading to agammaglobulinemia. Clin Immunol. 2025; 277 110503. doi: 10.1016/j.clim.2025.110503 Knox, AVC, Cominsky, LY, Sun, D, et al. One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them. Blood. 2025; 145 (22): 2549-2560. doi: 10.1182/blood.2024026683 Additional Declarations No competing interests reported. Supplementary Files SupplementalTables.docx Cite Share Download PDF Status: Published Journal Publication published 02 Mar, 2026 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 22 Oct, 2025 Reviews received at journal 16 Oct, 2025 Reviews received at journal 15 Oct, 2025 Reviews received at journal 30 Sep, 2025 Reviewers agreed at journal 30 Sep, 2025 Reviewers agreed at journal 29 Sep, 2025 Reviewers agreed at journal 28 Sep, 2025 Reviewers agreed at journal 28 Sep, 2025 Reviews received at journal 28 Sep, 2025 Reviewers agreed at journal 28 Sep, 2025 Reviewers agreed at journal 19 Sep, 2025 Reviewers agreed at journal 17 Sep, 2025 Reviewers invited by journal 17 Sep, 2025 Editor invited by journal 15 Sep, 2025 Editor assigned by journal 13 Sep, 2025 Submission checks completed at journal 13 Sep, 2025 First submitted to journal 04 Sep, 2025 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7538129","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":519238983,"identity":"00318ef5-1e76-4f5d-8106-511e9a18ac96","order_by":0,"name":"Ping Wu","email":"","orcid":"","institution":"First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Wu","suffix":""},{"id":519238984,"identity":"a615295b-785f-46f5-a536-524d69d29de4","order_by":1,"name":"Jing Zhao","email":"","orcid":"","institution":"First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Zhao","suffix":""},{"id":519238985,"identity":"dfbd5bf0-4b4d-4b02-a1c3-0d354525d61a","order_by":2,"name":"Zilong Yu","email":"","orcid":"","institution":"First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zilong","middleName":"","lastName":"Yu","suffix":""},{"id":519238986,"identity":"b0267921-cf21-4dc4-9c7c-f0485c921810","order_by":3,"name":"Hongwei Li","email":"","orcid":"","institution":"First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hongwei","middleName":"","lastName":"Li","suffix":""},{"id":519238987,"identity":"2c5cbf0b-4624-424c-b8ea-674d30b963be","order_by":4,"name":"Zhenwei Liu","email":"","orcid":"","institution":"First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhenwei","middleName":"","lastName":"Liu","suffix":""},{"id":519238988,"identity":"49cbf46c-529e-4b9a-8940-c02bb8dbd050","order_by":5,"name":"Yinghui Peng","email":"","orcid":"","institution":"First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yinghui","middleName":"","lastName":"Peng","suffix":""},{"id":519238989,"identity":"c0b37688-7217-4aa5-893b-509bdb5cc208","order_by":6,"name":"Zhe Cai","email":"","orcid":"","institution":"Guangzhou Women and Children Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Zhe","middleName":"","lastName":"Cai","suffix":""},{"id":519238990,"identity":"aa6d67e1-65a1-436c-ac76-dfe96da543ca","order_by":7,"name":"Dehui Chen","email":"","orcid":"","institution":"First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Dehui","middleName":"","lastName":"Chen","suffix":""},{"id":519238991,"identity":"5872b83f-7d12-433e-9188-3610f543b540","order_by":8,"name":"Chengyu Lu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBAC9mYGNoYHDBJy9sebDxCnhecwUEsCg4Uxw5ljCURqOQDWUpHYcCPHgEgt7OzPHiS2SSQ2NuR8vPGGwU5Ot4GQFmYecwOgFuNmhrObLecwJBubHSCgxZ6Zh00CqEW2jbF3mzQPw4HEbYS08DCzPwNpYexh5nlGrBYGM5AWxRlsPGzEauExk0g4J2FswMNmbDnHgAi/8PAffybxoaxOzkD+8cMbbyrs5AhqQQESPERGDbIWUnWMglEwCkbBiAAA11w6NWxIb0EAAAAASUVORK5CYII=","orcid":"","institution":"First Affiliated Hospital of Guangzhou Medical University","correspondingAuthor":true,"prefix":"","firstName":"Chengyu","middleName":"","lastName":"Lu","suffix":""}],"badges":[],"createdAt":"2025-09-04 16:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7538129/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7538129/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-06498-4","type":"published","date":"2026-03-02T15:57:51+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":92274578,"identity":"9cdbeabd-7e9b-4b04-82f3-56050c3f1937","added_by":"auto","created_at":"2025-09-26 15:27:19","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1504330,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/7f122cb3052b4ca89eca6e16.docx"},{"id":92274681,"identity":"64305901-665e-4bfc-bb5d-dac59cf27aff","added_by":"auto","created_at":"2025-09-26 15:27:31","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":10430,"visible":true,"origin":"","legend":"","description":"","filename":"484a1610f7d443f3bf0beba9a7d9a383.json","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/7c15d6c1abda0a4baa59efb3.json"},{"id":92274633,"identity":"7ef2833d-f3c9-413b-9482-e59968b2c3d0","added_by":"auto","created_at":"2025-09-26 15:27:29","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":30124,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/36a4b3cf4473f9b24fdf1931.docx"},{"id":92274634,"identity":"55b8ad37-71b1-4ea4-a890-783304c0a91b","added_by":"auto","created_at":"2025-09-26 15:27:29","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":114196,"visible":true,"origin":"","legend":"","description":"","filename":"484a1610f7d443f3bf0beba9a7d9a3831enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/a573b17ce2f90f0e89584e12.xml"},{"id":92274662,"identity":"3d885bfe-2b6c-4f78-928e-ec3565a35ada","added_by":"auto","created_at":"2025-09-26 15:27:30","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":648607,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/9dc8276246215fbfe5a56f80.jpeg"},{"id":92274791,"identity":"369d779c-64ce-454d-889c-0db2d3342963","added_by":"auto","created_at":"2025-09-26 15:27:39","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":895453,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/93d7b4584f87c2527e6434cd.jpeg"},{"id":92274654,"identity":"f9a72766-f091-43ea-974a-c56c9106c8f4","added_by":"auto","created_at":"2025-09-26 15:27:30","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":154412,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/87eacb0c717bad341b1890c9.png"},{"id":92274635,"identity":"89244988-e3f9-460a-a225-7ba988fb4ffb","added_by":"auto","created_at":"2025-09-26 15:27:29","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":195934,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/309d688123282e64a365f1f1.png"},{"id":92274668,"identity":"281f2fb2-1c89-403a-a989-539f08c181b0","added_by":"auto","created_at":"2025-09-26 15:27:31","extension":"xml","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":112906,"visible":true,"origin":"","legend":"","description":"","filename":"484a1610f7d443f3bf0beba9a7d9a3831structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/930a124dcc4f991a5340645a.xml"},{"id":92274581,"identity":"ca71cecf-e502-4d64-beb8-fce125b85628","added_by":"auto","created_at":"2025-09-26 15:27:19","extension":"html","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":121650,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/be3be5b42fc2a8c833b56672.html"},{"id":92274598,"identity":"91ce5fd3-3c76-4088-924b-19276486d00f","added_by":"auto","created_at":"2025-09-26 15:27:22","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":400721,"visible":true,"origin":"","legend":"\u003cp\u003eGenetic and Clinical Characteristics of the Patient with Agambulinemia. A. Results of high-precision whole exome PLUS sequencing of the patient’s family. The table shows that the SPI1 gene (OMIM: 619707) follows an autosomal dominant (AD) inheritance pattern. The variant is derived from the mother, with a nucleotide variation of c.566T\u0026gt;C (HG19 position: chr11:47377025) corresponding to an amino acid change of p.Ile189Thr. The zygosity status is heterozygous, the ACMG variant classification is of uncertain significance (Unclear Meaning), and the related disease is agammaglobulinemia type 10. B. Pedigree chart of the Chinese family with patient carring the heterozygous variat SPI1 c.566T\u0026gt;C (p.Ile189Thr). Half-blue symbols represent healthy carriers with heterozygous mutations, which refer to patients with autosomal dominant disease. Square denotes male, circles represent females, and the black arrow indicates the proband (the affected child). C. Sanger sequencing chromatograms of genomic cDNA, \u0026nbsp;confirming the presence of aforementioned heterozygous variant in the patient (the variant site is marked with an arrow). D. Coronal CT scan of the paranasal sinuses. Red triangles mark the typical inflammatory manifestations of the bilateral maxillary sinuses and ethmoid sinuses. E. Red triangle marks to the inflammatory manifestation of the right frontal sinus. F. Red triangles mark the typical inflammation of bilateral sethmoid sinuses.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/17b825b740b1d7ed8376733e.jpeg"},{"id":92274643,"identity":"b34c9ead-e694-418c-a3ae-2142331e9781","added_by":"auto","created_at":"2025-09-26 15:27:30","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":430898,"visible":true,"origin":"","legend":"\u003cp\u003eResults of Chest CT and Bronchoendoscopy.Figure 2. A. Red arrow shows inflammatory nodule in the lower lobe of the right lung. B. Red arrow indicates lung abcess in the right lung. C. Red arrow points to bronchiectasia in the left lung. D. Yellow arrows mark the distribution of sputum in different lung lobes, including the tracheal carina, left principal bronchus, left lower lobe, and bronchus intermedius.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/1f521f57db9177c54c7d4d94.jpeg"},{"id":104251982,"identity":"6a0ee929-d189-4995-876b-44a2e41cf167","added_by":"auto","created_at":"2026-03-09 16:16:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1802324,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/af9c29aa-7737-45a9-bbd5-5983779b74df.pdf"},{"id":92274628,"identity":"563cce97-334d-41f2-9c05-b6fa7dce7c32","added_by":"auto","created_at":"2025-09-26 15:27:29","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":30124,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7538129/v1/3bbd121833bb6a4c93bdbd69.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Novel Mutations of the SPI1 Gene in a Chinese Girl with Agammaglobulinemia","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAgammaglobulinemia, as a primary immunodeficiency disease, is mainly characterized by a severe reduction or absence of B lymphocytes in peripheral blood, which in turn leads to low or near deficiency of serum immunoglobulin levels[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Clinically, patients usually present with recurrent rhinosinusitis and pulmonary infections[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In severe cases, systemic infections may occur, posing a serious threat to health and survival[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. X-linked agammaglobulinemia (XLA) is one of the most common primary immunodeficiency disorders in children, exhibiting X-linked recessive inheritance, with most patients being male[\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Beyond XLA, autosomal dominant and recessive forms of agammaglobulinemia also exist[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]; these are rarer, with fewer associated studies.\u003c/p\u003e\u003cp\u003eThis report describes a case of autosomal dominant angammaglobulinemia caused by a SPI1 gene mutation, enriching the genotypic spectrum of angammaglobulinemia and providing new data for research on this disease. Through detailed analysis of this case, we aim to deepen understanding of autosomal dominant angammaglobulinemia and offer valuable references for clinical diagnosis and treatment.\u003c/p\u003e"},{"header":"Clinical Information","content":"\u003cp\u003eA 13-year-old girl was admitted due to cough and fever lasting over 1 week. She had experienced recurrent lower respiratory tract infections since the age of 2, approximately once every 2 months. Two months prior, she was treated in the pediatric intensive care unit (PICU) for severe pneumonia lasting 1 month. She was born to prematurely via natural delivery at 34 weeks of gestation, with a birth weight of 2.6 kg. Her parents were healthy, non-consanguineous, and denied any family history of genetic diseases.\u003c/p\u003e\u003cp\u003ePhysical examination revealed coarse breath sounds in both lungs, with scattered fine moist rales. Her growth and development were normal. Laboratory tests showed significantly elevated infammatory markers (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), decreased total protein and albumin(Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), markedly reduced IgG and IgA, and a B lymphocyte ratio (CD3\u003csup\u003e−\u003c/sup\u003eCD19\u003csup\u003e+\u003c/sup\u003e)/ lymphocytes and absolute B cell count of 0 (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Cytokine profiles are shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, supporting a preliminary diagnosis of immune deficiency. Genetic testing of the patient, her younger brother, and parents revealed heterozygous mutations c.566T \u0026gt; C and p.Ile189Thr in the patient’s SPI1 gene (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Further analysis confirmed that the mutation was inherited from her mother; neither her father nor brother carried it (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB-C).\u003c/p\u003e\u003cp\u003eParanasal sinus CT scans showed inflammation in both maxillary sinuses, ethmoid sinuses and the right frontal sinus (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD-F). Chest CT scans revealed extensive bilateral pulmonary inflammation, with inflammatory nodules in the apical posterior segment of the left upper lung and the extrapulmonary basal segment of the left lower lung (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-C). Bronchoscopy detected copious sputum in multiple lung lobes, including the tracheal carina, left main bronchus, left lower lobe, and bronchus intermedius (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical characteristics of blood diagnostics ( n = 6), median (IQR)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameters\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMeasured values\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNormal range\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute number of white blood cell, median (IQR), 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.58 (5-30.36)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.5–9.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute number of neutrophil, median (IQR), 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.2(3.02–26.7)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.8–6.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePercentage of neutrophil, median (IQR), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65.74 (43.7–87.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40–75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute number of lymphocytes, median (IQR), 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.42 (1.39–3.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.1–3.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePercentage of lymphocytes, median (IQR), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.68 (7.4–42.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20–50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute number of monocytes, median (IQR), 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.81(0.39–1.3)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1–0.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePercentage of monocyte, median (IQR), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.83(4.3–10.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.0–10.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute number of red blood cell, median (IQR), 10\u003csup\u003e12\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.84 (4.38–5.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.8–5.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin, median (IQR), g/l\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e122.33 (114–132)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e115–150\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHematocrit, median (IQR), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38.2 (34–41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35–45\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean hemoglobin amount, median (IQR), pg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25.25 (24-25.7)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27–34\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean hemoglobin concentration, median (IQR), g/l\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e324.83 (319–340)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e316–354\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelet, median (IQR), 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e249.33(168–312)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e126–350\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelet distribution width, median (IQR), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42.04(35.5-48.13)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.0–17.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC-reactive protein, median (IQR), mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.04(0.72–7.4)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-0.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe table shows the statistically significant differences between measurement results and normal range (p \u0026lt; 0.05). \u003csup\u003ea\u003c/sup\u003e The values higher than normal range. \u003csup\u003eb\u003c/sup\u003e The values are lower than normal range.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical characteristics of biochemical detection indices ( n = 4), median (IQR)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameters\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMeasured values\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNormal range\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAspartate amino transferase, median (IQR), U/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17.43(11.7–24.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13–35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatine kinase, median (IQR), U/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45.6(40-51.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40–200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatine kinase isoenzyme, median (IQR), U/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17(15–20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.0–25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLactate dehydrogenase, median (IQR), U/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e174.67(131–236)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e120–250\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh-sensitivity troponinⅠ, median (IQR), pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.7(2-4.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-17.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMyohemoglobin, median (IQR), ug/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.13(5.7-7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlkaline phosphatase, median (IQR), U/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e143.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81–454\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlanine aminotransferase, median (IQR), U/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13.1(5.8–26.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7–40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal protein, median (IQR), g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59.6(56.7–63.6)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65–85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin, median (IQR), g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39.38 (35.8–42.2)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40–55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNatrium, median (IQR), mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e140.6(139.8–142)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e135–145\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKalium, median (IQR), mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.74(3.35–4.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.5-5.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChlorinum, median (IQR), mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e106.27(105.1–109)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e99–110\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium, median (IQR), mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.27 (2.18–2.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.24–2.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c4\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCreatinine, median (IQR), µmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41.17(37.8–47.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33–75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe table shows the statistically significant differences between measurement results and normal range (p \u0026lt; 0.05). \u003csup\u003ea\u003c/sup\u003e The values higher than normal range. \u003csup\u003eb\u003c/sup\u003e The values are lower than normal range.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical characteristics of immune-related indices ( n = 5), median (IQR).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameters\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMeasured values\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNormal range\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgG, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.94(2.89–5.09)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.0–16.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgA, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0(0-0.01)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.7-5.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgM, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.57(0.15–0.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.4–2.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC3, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.15(1.05–1.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.9–1.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC4, g/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.28(0.28–0.32)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1–0.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eB cells/lymphocytes (CD19+), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.03 (0-0.1)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5–18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute count of B cells (CD19 + Abs), cells/uL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(0–3)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e90–560\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eT cells/lymphocytes (CD3+/CD45+), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e84.3 (81.3–90.5)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50–84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute count of T cells (CD3 + Abs), cells/uL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2231 (1361–2729)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e955–2860\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHelper T cells/lymphocytes (CD3+/CD4+), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.86(18.7–25.7)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30–60\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute count of helper T cells (CD3+/CD4 + Abs), cells/uL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e686.67(411–832)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e550–1440\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInhibit T cells/lymphocytes (CD3+/CD8+), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50.96(46.4–65.1)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13–41\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute count of inhibit T cells (CD3+/CD8 + Abs), cells/uL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1265.33(775–1550)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e320–1250\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNK cells/lymphocytes (CD16+/CD56+), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16.27(14.5–17.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7–40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute count of NK cells (NK Abs), cells/uL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e447.33(234–560)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e150–1100\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe table shows the statistically significant differences between measurement results and normal range (p \u0026lt; 0.05). The measurement results with red color are the values higher than normal range. The blue ones are lower than normal range. The black ones are in the normal range.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical characteristics of cytokines ( n = 3), median (IQR).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameters\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMeasured values\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNormal range\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIL-5, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.77(0.36–1.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-3.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIL-17A, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.74 (0.63–2.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-20.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIL-1β, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.42 (0.82–4.08)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-12.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIL-2, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.08 (0.79–1.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-5.71\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIL-4, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.90 (0.58–1.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-2.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIL-6, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e384.81 (12.45-1126.9)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-5.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIL-8, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e508.56 (9.44-1238.7)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-20.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIL-10, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18.20 (1.52–49.11)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-4.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIL-12p70, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.64 (0.68–2.18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-3.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTNF-α, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.23 (0.37–1.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-4.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTNF-β, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.71(0.75–2.19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-7.42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIFN-γ, pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.5 (2.11–2.92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0-4.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe table shows the statistically significant differences between measured values and normal range (p \u0026lt; 0.05).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eTreatment results and prognosis\u003c/h3\u003e\n\u003cp\u003eFollowing active anti-infection therapy, intravenous gamma globulin infusion, bronchoscopic lavage, and supportive care, the patient's condition improved gradually. Her body temperature normalized, and after over 72 hours, cough and expectoration significantly diminished. Pulmonary nodules resolved, and inflammatory markers(e.g., white blood cell count and C-reactive protein) returned to normal ranges. Follow-up chest and paranasal sinus CT scans showed marked absorption of pulmonary inflammation, reduced inflammatory nodules and lung abcess, and alleviated paranasal sinus inflammation. The patient’s mental status snd appetite improved, with stable vital signs, meeting discharge criteria. After discharge, she received intravenous gamma globulin (6g) every 4 weeks. During follow-up, no severe infections (e.g., sepsis, meningitis) occurred, and her growth and development gradually normalized.\u003c/p\u003e\n\u003ch3\u003eLiterature review\u003c/h3\u003e\n\u003cp\u003eWe searched PubMed using the keywords \u0026ldquo;agammaglobulinemia\u0026rdquo;, \u0026ldquo;X-linked\u0026rdquo;, \u0026ldquo;autosomal dominant\u0026rdquo;, and \u0026ldquo;autosomal recessive\u0026rdquo;, reviewing English and Chinese literature from 1965 to 2025. Studies identifying associated genes were included, and differences among patients from various continents were analyzed (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Supplemental Table\u0026nbsp;4).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAutosomal genetic characteristics of agammaglobulinemia patients across different countries.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCountry\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChina[\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSwitzerland[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eUnited Kingdom[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRepublic of Serbia[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eJapan[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eAustralia[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eUSA[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutosomal Dominant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eheterozygous mutationof TCF3 gene\u003c/b\u003e: c.1663G\u0026thinsp;\u0026gt;\u0026thinsp;A(p.E555K);\u003c/p\u003e\u003cp\u003e\u003cb\u003emutation of the STAT1 gene\u003c/b\u003e: c.1154 C\u0026thinsp;\u0026gt;\u0026thinsp;T; c.821G\u0026thinsp;\u0026gt;\u0026thinsp;A(p.R274Q);\u003c/p\u003e\u003cp\u003e\u003cb\u003eheterozygous mutationof NFKB2 gene\u003c/b\u003e: c.2540dupT\u003c/p\u003e\u003cp\u003e\u003cb\u003emutation of the PIK3CD gene\u003c/b\u003e: c.3061G\u0026amp;gt;A(E1021K);\u003c/p\u003e\u003cp\u003ec.3061G\u0026gt;A;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003emonoallelic LIG4 missense mutations\u003c/b\u003e: c.G1739A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003emutation of the CTLA4 gene\u003c/b\u003e: c.105C\u0026thinsp;\u0026gt;\u0026thinsp;A(p.035*);\u003c/p\u003e\u003cp\u003ec.110\u0026thinsp;+\u0026thinsp;1G\u0026thinsp;\u0026gt;\u0026thinsp;T;\u003c/p\u003e\u003cp\u003ec.208C\u0026thinsp;\u0026gt;\u0026thinsp;T(p.R70W);\u003c/p\u003e\u003cp\u003ec.371A\u0026thinsp;\u0026gt;\u0026thinsp;C(p.T124P);\u003c/p\u003e\u003cp\u003eс.223C\u0026thinsp;\u0026gt;\u0026thinsp;T(p.R75W);\u003c/p\u003e\u003cp\u003ec. 2T\u0026thinsp;\u0026gt;\u0026thinsp;C;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003emutation of the\u003c/b\u003e \u003cb\u003eSPI1\u003c/b\u003e \u003cb\u003egene\u003c/b\u003e: c.441dup;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003emutation of the TCF3 gene\u003c/b\u003e: c.1663G\u0026thinsp;\u0026gt;\u0026thinsp;A(p.E555K);\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003emutation of the NFKB2 gene\u003c/b\u003e: c.2594A\u0026thinsp;\u0026gt;\u0026thinsp;G;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eheterozygous mutationof SPI1 gene\u003c/b\u003e: c.325_327delGGCinsAG(p.G109Sfs*78);\u003c/p\u003e\u003cp\u003ec.331C\u0026thinsp;\u0026gt;\u0026thinsp;T(p.Q111X);\u003c/p\u003e\u003cp\u003ec.366C\u0026thinsp;\u0026gt;\u0026thinsp;A(p.Y122X);\u003c/p\u003e\u003cp\u003ec.635A\u0026thinsp;\u0026gt;\u0026thinsp;C(p.H212P);\u003c/p\u003e\u003cp\u003ec.696_697delGC(p.L233Afs*53);\u003c/p\u003e\u003cp\u003ec.725T\u0026thinsp;\u0026gt;\u0026thinsp;G(p.V242G);\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCountry\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eSharjah\u003c/b\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eIran\u003c/b\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eChina\u003c/b\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eArgentinia\u003c/b\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eUSA\u003c/b\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eSweden\u003c/b\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eSpan\u003c/b\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003eItaly\u003c/b\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAutosomal Recessive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003emutation of the PIK3R1 gene\u003c/b\u003e: c.244dup(p.(lle82Asnfs*24)chr5: 67522740)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003emutation of the IGLL1 gene\u003c/b\u003e: c.258delG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003emutation of the \u0026micro;HC gene\u003c/b\u003e: c.1956G\u0026thinsp;\u0026gt;\u0026thinsp;A;\u003c/p\u003e\u003cp\u003e\u003cb\u003eheterozygous mutationof DNMT38 gene\u003c/b\u003e: c.2477G\u0026thinsp;\u0026gt;\u0026thinsp;A(p.R826H)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003emutation of the IGHM gene\u003c/b\u003e: c.258G\u0026gt;A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003emutation of the IGHM gene\u003c/b\u003e: c.433G\u0026gt;A;\u003c/p\u003e\u003cp\u003ec.412T\u0026gt;G;\u003c/p\u003e\u003cp\u003e\u003cb\u003eDefects in the mu heavy-chain gene\u003c/b\u003e: c.1768T\u0026gt;G\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003emutation of the IGHM gene\u003c/b\u003e: c.433G\u0026gt;A;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003emutation of the IGHM gene\u003c/b\u003e: c.168AAdel;\u003c/p\u003e\u003cp\u003ec.433G\u0026gt;A;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003emutation of the IGHM gene\u003c/b\u003e: c.433G\u0026gt;A;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn rare disease research, agammaglobulinemia-a primary immunodeficiency disorder- has long been a focus of global scholars. XLA, with its relatively high incidence and clear genetic mechanism, has been extensively studied[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Since Bruton first reported XLA in 1952, numerous studies have been conducted worldwide[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. XLA is caused by mutations in the gene encoding Bruton's tyrosine kinase (BTK) on the X chromosome, disrupting B cell differentiation and maturation[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Most patients are male, presenting with recurrent bacterial infections, significantly reduced or absent serum immunoglobulins, and decreased circulating B lymphocytes[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. BTK mutations are detectable in 80% \u0026minus;\u0026thinsp;90% of clinically diagnosed cases[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], including single-nucleotide deletions, substitutions, insertions, frameshift, nonsense, and missense mutations[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn contrast, research on autosomal dominant or recessive agammaglobulinemia began later. Due to rarity, such studies are challenging but have made progress in recent years. Through studies of agammaglobulinemia patients, international scholars have identified multiple autosomal recessive mutations, including those in \u0026micro;HC, PIK3R1, TCF3, and SLC39A7[\u003cspan additionalcitationids=\"CR38 CR39\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. These mutations impair genes regulating early B cell differentiation and function, triggering agammaglobulinemia. Patients with autosomal recessive agammaglobulinemia (ARA) exhibit earlier onset and higher susceptibility to severe complications[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRegarding SPI1 mutations and agammaglobulinemia, researchers at Children's Hospital of Philadelphia performec exome sequencing on 30 global patients with absent B lymphocytes, finding SPI1 mutations in 6 cases[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. SPI1 encodes the PU.1 protein, which plays a critical role in B lymphocyte development by facilitating chromatin accessibility in bone marrow B cells[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. PU.1 deficiency blocks this accessibility, preventing B cell formation and causing agammaglobulinemia[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. In vitro CRISPR-based studies confirmed the roles of SPI1 and PU.1, revealing B cells\u0026rsquo; high sensitivity to PU.1 perturbations[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite progress, many aspects of agammaglobulinemia remain unclear, particularly the molecular mechanisms by which SPI1 mutations cause the disease and the development of more effective treatments, requiring further research.\u003c/p\u003e\u003cp\u003eThis study employed multiple methods to ensure scientific rigor: detailed recording and analysis of the patient\u0026rsquo;s medical history, clinical manifestations, laboratory results, and genetic data to clarify desease progression, providing direct clinical evidence; and comprehensive review of domestic and international literature to contextualize research status and progress, offering theoretical support.\u003c/p\u003e\u003cp\u003eThe key innovation lies in identifying a novel autosomal dominant agammaglobulinemia mutation: whole-exome sequencing revealed heterozygous SPI1 mutations (c.566T\u0026thinsp;\u0026gt;\u0026thinsp;C, p.Ile189Thr), unreported previously, enriching the disease\u0026rsquo;s genotypic spectrum. Additionally, this case highlights the possibility of congenital agammaglobulinemia in females. While X-linked agammaglobulinemia predominantly affects males, this female patient-carrying a maternally inherited mutation\u0026mdash;demonstrates that autosomal dominant inheritance can affect females, broadening understanding of the disease\u0026rsquo;s genetic characteristics.\u003c/p\u003e\u003cp\u003eThis single-case study provides new insights and data for autosomal dominant agammaglobulinemia research but has limitations. The small sample size may introduce bias, failing to represent the full spectrum of autosomal dominant agammaglobulinemia. Limitations exist in analyzing incidence, clinical diversity, and treatment responses, hindering in-depth statistical analysis. Future research should collect more cases via multi-center collaboration to establish large cohorts, enabling comprehensive characterization of clinical features, genetics, and therapeutic efficacy. Large-scale studies could reveal disease patterns, risk factors, and treatment safety/effectiveness, strengthening clinical evidence.\u003c/p\u003e\u003cp\u003eWith advancing genetic testing, whole-exome sequencing is widely used in rare disease diagnosis. Future studies should enhance genetic testing for undiagnosed agammaglobulinemia patients to identify new pathogenic genes and mutations, investigate their mechanisms, and improve diagnostic accuracy. Exploring novel therapies\u0026mdash;such as gene editing to repair/replace mutated genes\u0026mdash;could offer curative potential, though challenges (e.g., precision, safety, ethics) in clinical application require resolution. Optimizing stem cell transplantation protocols to increase success rates and reduce complications may also expand treatment options.\u003c/p\u003e\u003cp\u003eFuture research should also address quality of life and mental health in agammaglobulinemia patients. Long-term treatment and life restrictions may induce anxiety or depression; studies should explore psychological support and social care strategies to improve quality of life, and optimize treatments to minimize disruption, facilitating social integration.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003egnomAD: Genome Aggregation Database; XLA: X-linked agammaglobulinemia; PICU: pediatric intensive care unit; \u0026nbsp;BTK: Bruton\u0026apos;s tyrosine kinase; ARA: Autosomal recessive agammaglobulinemia.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe thank the family of the reported individual, Guangzhou Amcare Genomic Laboratory and colleagues from the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed and critically revised the manuscript. PW, DHC and CYL conceptualized the idea; PW, JZ and ZC drafted the manuscript and revised the manuscript; ZLY, HWL, ZWL and YHP collected the data. All authors approved of the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Western Medicine-General Guide \u0026nbsp;Item of Guangzhou Municipal Health Commission (No. \u0026nbsp; 20241A011039).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the ethical committees of the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China. Written informed consent of this study was obtained from his parents of this patient.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent of this case report obtained from his parents of this patient was approved for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Pediatrics, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, Guangdong, China. \u003csup\u003e2\u003c/sup\u003eGuangzhou Institute of Pediatrics, Guangzhou Women and Children\u0026rsquo;s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China. \u003csup\u003e3\u003c/sup\u003eDepartment of Allergy, Immunology and Rheumatology, Guangzhou Women and Children\u0026rsquo;s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eKhoshnevisan, R, Hassanzadeh, S, Klein, C, et al. B-cells absence in patients diagnosed as inborn errors of immunity: a registry-based study. IMMUNOGENETICS. 2024; 76 (3): 189-202. doi: 10.1007/s00251-024-01342-y\u003c/li\u003e\n \u003cli\u003eMarkocsy, A, Kapustov\u0026aacute;, D, Čere\u0026scaron;, A, et al. Atypical Manifestation of X-linked Agammaglobulinemia - the Importance of Genetic Testing. Acta Medica (Hradec Kralove). 2024; 67 (2): 60-63. doi: 10.14712/18059694.2024.21\u003c/li\u003e\n \u003cli\u003eKaradeniz, EB, Aliyeva, C, Aydemir, S, et al. Chronic Rhinosinusitis in Patients with Primary Immunodeficiency. INT ARCH ALLERGY IMM. 2022; 184 (3): 302-310. doi: 10.1159/000527265\u003c/li\u003e\n \u003cli\u003eIvankovich‐Escoto, G, Danielian, S, Morera, E, et al. Clinical, immunological and genetic characterization of patients with X‐linked agammaglobulinemia in Costa Rica SCAND J IMMUNOL. 2022; 97 (1): doi: 10.1111/sji.13237\u003c/li\u003e\n \u003cli\u003eThangaraj, A, Sil, A, Goel, S, et al. Disseminated Aspergillosis in X-linked Agammaglobulinemia: Beyond the norm. J CLIN IMMUNOL. 2024; 45 (1): 24. doi: 10.1007/s10875-024-01815-5\u003c/li\u003e\n \u003cli\u003eMadathil Govindaraj, G, Jain, A, Edavazhippurath, A, et al. Clinical, immunological and genomic characteristics of children with X-linked agammaglobulinemia from Kerala, South India. HUM IMMUNOL. 2022; 83 (4): 335-345. doi: 10.1016/j.humimm.2022.01.003\u003c/li\u003e\n \u003cli\u003eCardenas-Cruz, C, Jim\u0026eacute;nez-Santana, L, Campos-Lopez, D, et al. X-linked agammaglobulinemia: 35 years of experience in a tertiary pediatric hospital in Latin America Int J Contemp Pediatrics. 2022; doi: 10.18203/2349-3291.ijcp20223151\u003c/li\u003e\n \u003cli\u003eAltman, K, Zhou, C, Hernandez-Trujillo, V, et al. Health-Related Quality of Life in 91 Patients with X-Linked Agammaglobulinemia. J CLIN IMMUNOL. 2022; 42 (4): 811-818. doi: 10.1007/s10875-022-01222-8\u003c/li\u003e\n \u003cli\u003ePatel, S, Roberts, R. Transient Hypogammaglobulinemia of Infancy, a Possible Autosomal Dominant Inheritance Pattern in Certain Families J ALLERGY CLIN IMMUN. 2006; 117 (2): S172. doi: 10.1016/j.jaci.2005.12.685\u003c/li\u003e\n \u003cli\u003eCardenas-Morales, M, Hernandez-Trujillo, VP. Agammaglobulinemia: from X-linked to Autosomal Forms of Disease. CLIN REV ALLERG IMMU. 2021; 63 (1): 22-35. doi: 10.1007/s12016-021-08870-5\u003c/li\u003e\n \u003cli\u003eXu Yingyang et al., A case of autosomal dominant agammaglobulinemia. Chinese Journal of Clinical Immunity and Allergy, 2021. 15(3): p.322-324.\u003c/li\u003e\n \u003cli\u003eChen Lanqin et al., Two Chinese cases with STAT1 gene gain-of-function variation. Chinese Journal of Pediatrics, 2021. 59(8): p.700-702.\u003c/li\u003e\n \u003cli\u003eWang Caihong et al., Two cases of congenital immunodeficiency with disseminated infection of cyanobacteria marneffei and literature review. Chinese Journal of Pediatric Emergency Medicine, 2020. 27(11): p.861-864.\u003c/li\u003e\n \u003cli\u003eZHENG Jing, XIAO Yangyang, LIU Liqun, et al. Activated PI3K-\u0026delta; syndrome caused by PIK3CD gene mutation: a case report and literature review[J]. Journal of Clinical Pediatrics, 2019, 37(4): p. 301-303.\u003c/li\u003e\n \u003cli\u003eWang Jialan, PIK3CD gene mutation induced PI3K\u0026delta; hyperactivation syndrome in children: a report of 2 cases and literature review Abstract, 2022, Qingdao University.\u003c/li\u003e\n \u003cli\u003eJauch, A.J., et al., Autoimmunity and immunodeficiency associated with monoallelic LIG4 mutations via haploinsufficiency. J Allergy Clin Immunol, 2023. 152(2): p. 500-516.\u003c/li\u003e\n \u003cli\u003eSchubert, D., et al., Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med, 2014. 20(12): p. 1410-1416.\u003c/li\u003e\n \u003cli\u003eMiskovic, R., et al., Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia. Front Immunol, 2024. 15: p. 1324679.\u003c/li\u003e\n \u003cli\u003eUtsumi, T., et al., Exclusive Characteristics of the p.E555K Dominant-Negative Variant in Autosomal Dominant E47 Deficiency. J Clin Immunol, 2024. 44(7): p. 167.\u003c/li\u003e\n \u003cli\u003eLee, C.E., et al., Autosomal-dominant B-cell deficiency with alopecia due to a mutation in NFKB2 that results in nonprocessable p100. Blood, 2014. 124(19): p. 2964-72.\u003c/li\u003e\n \u003cli\u003eLe Coz, C., et al., Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients. J Exp Med, 2021. 218(7).\u003c/li\u003e\n \u003cli\u003eSyed, I.J., et al., A Novel Variant of the PIK3R1 Gene Mutation Associated With SHORT Syndrome and \u0026nbsp; Agammaglobulinemia. Cureus, 2024. 16(6): p. e62983.\u003c/li\u003e\n \u003cli\u003eNaiboglu, S., et al., Single Mutation Different Clinical Findings: IGLL1 Defect. Iran J Allergy Asthma Immunol, 2024. 23(4): p. 452-456.\u003c/li\u003e\n \u003cli\u003eZhang Zhiyong et al., Analysis of mutation in heavy chain-\u0026mu; (\u0026mu;HC) gene in a Chinese patient with congenital agammaglobulinemia. Chinese Journal of Pediatrics, 2010. 48(4): p.279-283.\u003c/li\u003e\n \u003cli\u003eHu, S.C., et al., [Clinical and genetic manifestations of immunodeficiency, centromeric \u0026nbsp; instability, and facial anomalies syndrome: a case report and literature review]. Zhonghua Er Ke Za Zhi, 2019. 57(1): p. 55-59.\u003c/li\u003e\n \u003cli\u003eLopez, G.E., et al., Clinical and molecular analysis of patients with defects in micro heavy chain \u0026nbsp; gene. J Clin Invest, 2002. 110(7): p. 1029-35.\u003c/li\u003e\n \u003cli\u003eYel, L., et al., Mutations in the mu heavy-chain gene in patients with agammaglobulinemia. N Engl J Med, 1996. 335(20): p. 1486-93.\u003c/li\u003e\n \u003cli\u003eTeocchi, M, de Andrade Eug\u0026ecirc;nio, T, Furlaneto Marega, L, et al. Dysregulation of Toll-Like Receptor Signaling-Associated Gene Expression in X-Linked Agammaglobulinemia: Implications for Correlations Genotype-Phenotype and Disease Expression. J INNATE IMMUN. 2024; 16 (1): 425-439. doi: 10.1159/000540082\u003c/li\u003e\n \u003cli\u003eConley, ME, Mathias, D, Treadaway, J, et al. Mutations in btk in patients with presumed X-linked agammaglobulinemia. AM J HUM GENET. 1998; 62 (5): 1034-43. doi: 10.1086/301828\u003c/li\u003e\n \u003cli\u003eYang, YD, Tang, H, Li, W, et al. Identification by whole-exome sequencing of novel mutation c.64C\u0026thinsp;\u0026gt;\u0026thinsp;G in the BTK gene of a fetus with X-linked agammaglobulinemia. ULTRASOUND OBST GYN. 2015; 45 (6): 753-4. doi: 10.1002/uog.14738\u003c/li\u003e\n \u003cli\u003eAlmutairy, KA, Alasmari, BG, Rayees, S. Digenic Inheritance of Hereditary Spherocytosis Type III and X-linked Agammaglobulinemia: Coexistence of Two Distinct Recessive Disorders in a Male Child. Cureus. 2024; 16 (9): e69887. doi: 10.7759/cureus.69887\u003c/li\u003e\n \u003cli\u003eBagheri, Y, Vosughi, A, Azizi, G, et al. Comparison of clinical and immunological features and mortality in common variable immunodeficiency and agammaglobulinemia patients. IMMUNOL LETT. 2019; 210 55-62. doi: 10.1016/j.imlet.2019.05.001\u003c/li\u003e\n \u003cli\u003eChung, M, Jung, J, Son, J, et al. A Case of X-Linked Agammaglobulinemia with Btk Gene Intron 2 Mutation TUBERC RESPIR DIS. 2008; 65 (3): 207. doi: 10.4046/trd.2008.65.3.207\u003c/li\u003e\n \u003cli\u003eIslam, TC, Smith, CI. The cellular phenotype conditions Btk for cell survival or apoptosis signaling. IMMUNOL REV. 2000; 178 49-63. doi: 10.1034/j.1600-065x.2000.17811.x\u003c/li\u003e\n \u003cli\u003eSaha, BK, Curtis, SK, Vogler, LB, et al. Molecular and structural characterization of five novel mutations in the Bruton\u0026apos;s tyrosine kinase gene from patients with X-linked agammaglobulinemia. MOL MED. 1997; 3 (7): 477-85. PMID: 9260159\u003c/li\u003e\n \u003cli\u003eZaidi, SK, Qureshi, S, Qamar, FN. X-linked agammaglobulinemia - first case with Bruton tyrosine kinase mutation from Pakistan. J PAK MED ASSOC. 2017; 67 (3): 471-473. PMID: 28304004\u003c/li\u003e\n \u003cli\u003eFerrari, S, Zuntini, R, Lougaris, V, et al. Molecular analysis of the pre-BCR complex in a large cohort of patients affected by autosomal-recessive agammaglobulinemia. Genes Immun. 2007; 8 (4): 325-33. doi: 10.1038/sj.gene.6364391\u003c/li\u003e\n \u003cli\u003eTang, P, Upton, JEM, Barton-Forbes, MA, et al. Autosomal Recessive Agammaglobulinemia Due to a Homozygous Mutation in PIK3R1. J CLIN IMMUNOL. 2017; 38 (1): 88-95. doi: 10.1007/s10875-017-0462-y\u003c/li\u003e\n \u003cli\u003eQureshi, S, Sheikh, MDA, Qamar, FN. Autosomal Recessive Agammaglobulinemia - first case with a novel TCF3 mutation from Pakistan. CLIN IMMUNOL. 2018; 198 100-101. doi: 10.1016/j.clim.2018.07.016\u003c/li\u003e\n \u003cli\u003eErdős, M, Mironska, K, Kareva, L, et al. A novel mutation in SLC39A7 identified in a patient with autosomal recessive agammaglobulinemia: The impact of the J\u0026nbsp;Project. PEDIAT ALLERG IMM-UK. 2022; 33 (6): e13805. doi: 10.1111/pai.13805\u003c/li\u003e\n \u003cli\u003eShillitoe, B, Gennery, A. X-Linked Agammaglobulinaemia: Outcomes in the modern era. CLIN IMMUNOL. 2017; 183 54-62. doi: 10.1016/j.clim.2017.07.008\u003c/li\u003e\n \u003cli\u003eRahmani, F, Aghamohammadi, A, Ochs, H, et al. Agammaglobulinemia: comorbidities and long-term therapeutic risks Expert Opin Orphan Drugs. 2017; 5 (7): 559-574. doi: 10.1080/21678707.2017.1330145\u003c/li\u003e\n \u003cli\u003eLe Coz, C, Nguyen, DN, Su, C, et al. Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients. J EXP MED. 2021; 218 (7): doi: 10.1084/jem.20201750\u003c/li\u003e\n \u003cli\u003eWahlster, L, Sankaran, VG. I SPI1 something needed for B cells. J EXP MED. 2021; 218 (7): doi: 10.1084/jem.20210572\u003c/li\u003e\n \u003cli\u003eMiskovic, R, Ljubicic, J, Bonaci-Nikolic, B, et al. Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia. Front Immunol. 2024; 15 1324679. doi: 10.3389/fimmu.2024.1324679\u003c/li\u003e\n \u003cli\u003eDaddali, R, Kettunen, K, Turunen, T, et al. Novel heterozygous SPI1c.538C\u0026gt;T p.(Leu180Phe) variant causes PU.1 haploinsufficiency leading to agammaglobulinemia. Clin Immunol. 2025; 277 110503. doi: 10.1016/j.clim.2025.110503\u003c/li\u003e\n \u003cli\u003eKnox, AVC, Cominsky, LY, Sun, D, et al. One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them. Blood. 2025; 145 (22): 2549-2560. doi: 10.1182/blood.2024026683\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Novel mutations, SPI1 gene, Agammaglobulinemia","lastPublishedDoi":"10.21203/rs.3.rs-7538129/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7538129/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Agammaglobulinemia is a rare immune disorder characterized by deficient immunoglobulin production, primarily affecting the B cells of the immune system.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Report:\u003c/strong\u003e \u0026nbsp;A 13-year-old girl was admitted to the hospital due to \"recurrent respiratory infections for over 6 years, accompanied by cough and fever for more than 1 week\". She had experienced recurrent fever, cough, and purulent sputum approximately once every 2 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInvestigation:\u003c/strong\u003e\u0026nbsp; Immunoglobulin testing revealed significantly decreased IgG and IgA levels, with both the ratio of B lymphocytes (CD3\u003csup\u003e-\u003c/sup\u003eCD19\u003csup\u003e+\u003c/sup\u003e)/ lymphocytes and the absolute B cell count being 0, leading to a preliminary diagnosis of immune deficiency.\u0026nbsp; Genetic testing was performed on the patient, her younger brother and their parents to determine the specific type of immune deficiency. Results showed that the patient carried a heterozygous mutation in the SPI1 gene (c.566T\u0026gt;C, p.Ile189Thr), confirming a diagnosis of autosomal dominant agammaglobulinemia. This mutation was inherited from her mother; neither her father nor her younger brother carried it. A literature review indicated that the c.566T\u0026gt;C mutation in the SPI1 gene had not been previously reported. Additionally, we summarized the clinical and genetic characteristics of patients from different continents. The patient received anti-infection treatment with piperacillin-tazobactam and voriconazole, intravenous gamma globulin infusion, bronchoscopic lavage, and symptomatic treatment (e.g., antipyretic, antitussive, expectorant, and nutritional support). Her condition improved rapidly, and she was discharged. Long-term follow-up showed that she received monthly intravenous gamma globulin infusions at a local hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis study reports a case of autosomal dominant agammaglobulinemia caused by a novel SPI1 gene mutation. To date, this mutation has not been recorded in Chinese reference gene databases or the global Genome Aggregation Database (gnomAD). Our findings suggest that whole-exome sequencing for detecting such mutations could improve the identification and early diagnosis of agammaglobulinemia, particularly in homozygous individuals with SPI1 mutations. These SPI1 mutations may represent a novel therapeutic target for the agammaglobulinemia in the future.\u003c/p\u003e","manuscriptTitle":"Novel Mutations of the SPI1 Gene in a Chinese Girl with Agammaglobulinemia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-26 15:03:10","doi":"10.21203/rs.3.rs-7538129/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-22T09:36:01+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-16T13:40:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-15T20:05:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-30T18:22:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"189609388597843088098474120506115789059","date":"2025-09-30T17:10:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"238977214173147100013172652074650205831","date":"2025-09-29T16:19:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"198281157834589269561506266440851318616","date":"2025-09-28T19:26:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"270144232929616618145565307165736862042","date":"2025-09-28T15:51:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-28T15:08:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"52333132085877595447371548860710960707","date":"2025-09-28T14:25:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"189353468111535792256194241974198561180","date":"2025-09-19T10:55:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"302549927825945851071619465291575741598","date":"2025-09-17T10:51:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-17T07:14:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-15T06:29:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-13T10:19:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-13T10:18:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2025-09-04T16:48:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a1319225-8ac2-44a9-bd72-8f1d34461b32","owner":[],"postedDate":"September 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T16:14:09+00:00","versionOfRecord":{"articleIdentity":"rs-7538129","link":"https://doi.org/10.1186/s12887-025-06498-4","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2026-03-02 15:57:51","publishedOnDateReadable":"March 2nd, 2026"},"versionCreatedAt":"2025-09-26 15:03:10","video":"","vorDoi":"10.1186/s12887-025-06498-4","vorDoiUrl":"https://doi.org/10.1186/s12887-025-06498-4","workflowStages":[]},"version":"v1","identity":"rs-7538129","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7538129","identity":"rs-7538129","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}