Molecular Genetics & Genomic Medicine最新文献_第9页

Association of a Homozygous TYMP c.131G>C Variant With MNGIE in a Chinese Pedigree: Insights From Genetic Analysis and Computational Modeling. 中国人家系TYMP C . 131g >C纯合变异与MNGIE的关联：来自遗传分析和计算模型的见解

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2026-06-01 DOI: 10.1002/mgg3.70253

Ling Li, Xiu Chen, Hua Li, Kai Guo, Ting Zhang, Mingyi Ma, Songhua Zhao

{"title":"Association of a Homozygous TYMP c.131G>C Variant With MNGIE in a Chinese Pedigree: Insights From Genetic Analysis and Computational Modeling.","authors":"Ling Li, Xiu Chen, Hua Li, Kai Guo, Ting Zhang, Mingyi Ma, Songhua Zhao","doi":"10.1002/mgg3.70253","DOIUrl":"10.1002/mgg3.70253","url":null,"abstract":"Background: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by mutations in TYMP, which disrupt thymidine metabolism. This study aimed to characterize a novel homozygous TYMP variant and provide insights into its potential structural and functional consequences through bioinformatic analyses.Methods: We identified a homozygous TYMP variant (c.131G>C, p.R44P) in a proband with MNGIE using whole-exome sequencing and Sanger sequencing. Computational structural analyses and molecular modeling were performed to predict the impact of the R44P substitution on thymidine phosphorylase (TP) stability, homodimerization, catalytic activity, and substrate binding.Results: The homozygous TYMP c.131G>C variant was confirmed in the proband. Computational analyses suggested that the p.R44P substitution may destabilize TP and potentially impair homodimerization. Molecular modeling further predicted altered thymidine binding and disrupted active-site geometry. These predicted perturbations are hypothesized to contribute to defective nucleotide metabolism, thymidine accumulation, and deoxynucleotide triphosphate pool imbalance, which may ultimately result in mitochondrial genomic instability manifesting as mitochondrial DNA deletions and depletion.Conclusion: Our findings report the TYMP c.131G>C variant in a homozygous configuration, extending beyond a recently described compound heterozygous case. The bioinformatic predictions support the classification of this variant as likely pathogenic in MNGIE, though functional studies are warranted to validate these findings.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"14 6","pages":"e70253"},"PeriodicalIF":1.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148272491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Identification and Functional Analysis of a Novel NSD2 Missense Variant in a Patient With Rauch-Steindl Syndrome". 更正“一种新的NSD2错义变异在Rauch-Steindl综合征患者中的鉴定和功能分析”。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2026-06-01 DOI: 10.1002/mgg3.70252

引用次数: 0

Identification of a Novel De Novo Heterozygous SEC61A1 Variant in a Patient With Severe Congenital Neutropenia. 重度先天性中性粒细胞减少症患者中一种新的从头杂合SEC61A1变异的鉴定

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2026-05-01 DOI: 10.1002/mgg3.70217

Zixuan Wang, Hui Jing, Yuhan Chen, Ling Zhong, Jiyun Yang

{"title":"Identification of a Novel De Novo Heterozygous SEC61A1 Variant in a Patient With Severe Congenital Neutropenia.","authors":"Zixuan Wang, Hui Jing, Yuhan Chen, Ling Zhong, Jiyun Yang","doi":"10.1002/mgg3.70217","DOIUrl":"10.1002/mgg3.70217","url":null,"abstract":"Background: Severe congenital neutropenia (SCN) is a heterogeneous hematopoietic disorder characterized by impaired granulocyte maturation and increased susceptibility to infections. Over 25 genes have been linked to SCN, yet the molecular pathogenesis remains unknown in 30%-50% of cases. This study aimed to expand the understanding of SEC61A1 variant-mediated diseases.Methods: Clinical data were collected from the patient. Whole-exome sequencing was performed, followed by Sanger sequencing for familial validation. Bioinformatics, conservation, and protein structural analyses were conducted to evaluate candidate variants.Results: We report an 11-year-old boy with decreased neutrophils and lymphocytes, and elevated proportions of monocytes and eosinophils. Bone marrow showed granulocytic hyperplasia with maturation arrest and nuclear abnormalities. Flow cytometric analysis of bone marrow cells is indicative of aberrant myeloid antigen differentiation and impaired granulocytic maturation. A novel de novo pathogenic SEC61A1 variant (c.1135 T > C; p.Trp379Arg) was identified. Structural analysis suggested that this variant may disrupt protein conformational stability.Conclusions: The SEC61A1 c.1135 T > C (p.Trp379Arg) variant is considered likely pathogenic. This is the second reported SEC61A1 variant associated with SCN11, expanding the genetic and phenotypic spectrum of SCN.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"14 5","pages":"e70217"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13128344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Confirmation of Exome Sequencing Results Using Sanger Sequencing-Considerations in a Low-Resource Setting. 使用Sanger测序确认外显子组测序结果-在低资源环境下的考虑。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2026-05-01 DOI: 10.1002/mgg3.70224

Nadja Louw, Samantha Schnell, Mhlekazi Molatoli, Ingrid Smit, Robyn Kerr, Koen Devriendt, Aimé Lumaka, Amanda Krause, Nadia Carstens, Zané Lombard

{"title":"Confirmation of Exome Sequencing Results Using Sanger Sequencing-Considerations in a Low-Resource Setting.","authors":"Nadja Louw, Samantha Schnell, Mhlekazi Molatoli, Ingrid Smit, Robyn Kerr, Koen Devriendt, Aimé Lumaka, Amanda Krause, Nadia Carstens, Zané Lombard","doi":"10.1002/mgg3.70224","DOIUrl":"10.1002/mgg3.70224","url":null,"abstract":"Background: Exome sequencing (ES) is now widely accepted as an appropriate first-tier diagnostic test for developmental disorders (DD). International guidelines recommend that in diagnostic settings, ES findings be validated with an orthogonal method, such as Sanger sequencing, before reporting. However, more recent guidance recognizes that confirmatory testing for variants meeting strict quality criteria is redundant. Weighing up the cost to benefit ratio of this practice is crucial in settings where ES is not routinely implemented. The Deciphering Developmental Disorders in Africa (DDD-Africa) study aims to enable equitable implementation of genomic medicine in low-resourced settings, focusing on using ES in resolving DD in Africa.Methods: We performed confirmatory Sanger sequencing for the first 64 probands (70 variants) that underwent ES in which a variant of interest was identified. Strict quality parameters were key to diminishing the observation of false-positive variants.Results: All high confidence variants identified by ES (n = 38) were confirmed using Sanger sequencing and low confidence variants (n = 32) were confirmed as false-positive.Conclusion: Confirming ES results with an orthogonal approach like Sanger sequencing is unnecessary in a resource-limited setting when robust, context-informed quality thresholds are applied. This recommendation removes significant barriers to the implementation of genomic medicine and allows for accelerated genomic access globally.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"14 5","pages":"e70224"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of a Novel Homozygous SCN1B Splice-Site Variant in a Consanguineous Families With Early-Onset Epilepsy: A Case Series and Review of Literature. 在早发性癫痫的近亲家族中鉴定一种新的纯合子SCN1B剪接位点变异：病例系列和文献综述

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2026-05-01 DOI: 10.1002/mgg3.70214

Anees Muhammad, Shafaq Ramzan, Hammad Yousaf, Rafia Zafar Ghumman, Farhan Bahadar Ali, Muhammad Athar Khalily, Asmat Ali, Wajid Ali, Salma Zia, Najeeb Ullah Khan, Muhammad Tahir Sarwar, Matias Toft, Zafar Iqbal, Ambrin Fatima

{"title":"Identification of a Novel Homozygous SCN1B Splice-Site Variant in a Consanguineous Families With Early-Onset Epilepsy: A Case Series and Review of Literature.","authors":"Anees Muhammad, Shafaq Ramzan, Hammad Yousaf, Rafia Zafar Ghumman, Farhan Bahadar Ali, Muhammad Athar Khalily, Asmat Ali, Wajid Ali, Salma Zia, Najeeb Ullah Khan, Muhammad Tahir Sarwar, Matias Toft, Zafar Iqbal, Ambrin Fatima","doi":"10.1002/mgg3.70214","DOIUrl":"10.1002/mgg3.70214","url":null,"abstract":"Background: Pathogenic variants in SCN1B, the gene encoding the sodium channel β1 subunit, are associated with generalized epilepsy with febrile seizures plus (GEFS+) and related epilepsy disorders. These disorders exhibit phenotypic heterogeneity and varying clinical severity under autosomal dominant as well as recessive inheritance models. The current study investigated the genetic basis of epilepsy in two consanguineous Pakistani families.Methods: We investigated two unrelated Pakistani families with four affected individuals presenting with early-onset epilepsy. Exome sequencing (ES) was performed in the index cases in both families to identify the underlying genetic cause. Sanger sequencing was used for validation and segregation analysis in additional family members.Results: The affected individuals presented overlapping clinical features including early-onset drug-refractory seizures, developmental delay, intellectual disability, and autism spectrum disorder. ES identified a novel homozygous canonical splice-site variant in SCN1B (NM_001037.5): c.591-2A>G p.(?) in all affected individuals.Conclusions: A novel homozygous SCN1B splice site variant was identified in two unrelated consanguineous families as the most likely cause of the early-onset epilepsy. These findings underscore the importance of genetic screening and tailored therapeutic strategies in epilepsy management.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"14 5","pages":"e70214"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pedigree and Functional Analysis of Two Cryptic OTC Variants Causing Ornithine Transcarbamylase Deficiency in Two Unrelated Chinese Male Patients. 两例无亲缘关系的中国男性鸟氨酸转甲氨基酰基酶缺乏症的两种OTC隐性变异的家系和功能分析。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2026-05-01 DOI: 10.1002/mgg3.70223

Qingming Wang, Huimin Xiao, Fang Zhang, Hui Li, Juan Zhao, Haiming Yuan

{"title":"Pedigree and Functional Analysis of Two Cryptic OTC Variants Causing Ornithine Transcarbamylase Deficiency in Two Unrelated Chinese Male Patients.","authors":"Qingming Wang, Huimin Xiao, Fang Zhang, Hui Li, Juan Zhao, Haiming Yuan","doi":"10.1002/mgg3.70223","DOIUrl":"10.1002/mgg3.70223","url":null,"abstract":"Background: Ornithine transcarbamylase deficiency (OTCD, MIM#311250) is a rare X-linked urea cycle disorder causing hyperammonemia. While around 600 pathogenic OTC variants have been reported, cryptic changes like synonymous or in-frame variants remain poorly characterized and are easily overlooked in routine screening.Methods: We analyzed the clinical and genetic profiles of two unrelated Chinese male patients clinically diagnosed with OTCD. Whole-exome sequencing (WES) was performed to identify the genetic etiology. A minigene assay was then used to assess the splicing effect of the detected synonymous variant.Results: WES revealed two rare OTC variants: a synonymous variant (NM_000531.6: c.663G>A, p.Lys221Lys) and a novel de novo inframe variant (c.756_761dupAGCAGC, p.Ala253_Ala254dup). Minigene assay confirmed that the c.663G>A variant causes exon 6 skipping, leading to the deletion of 41 amino acids (c.541_663del, p.Glu181_Lys221del). Both variants were classified as clinically pathogenic, and the genotype-phenotype relationships were potentially established.Conclusion: Our study expands the mutation spectrum of OTC and emphasizes the importance of cryptic variants interpretation and the need for additional functional studies to verify the pathogenicity of these variants.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"14 5","pages":"e70223"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GPIHBP1 Autoantibody-Related Hypertriglyceridemia in Children: A Report of Two Cases and a Review of Pediatric Cases From the Literature. 儿童GPIHBP1自身抗体相关的高甘油三酯血症：两例报告和儿科病例文献综述

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2026-05-01 DOI: 10.1002/mgg3.70228

Rai-Hseng Hsu, Wuh-Liang Hwu, Feng-Jung Yang, Ni-Chung Lee, Yin-Hsiu Chien

{"title":"GPIHBP1 Autoantibody-Related Hypertriglyceridemia in Children: A Report of Two Cases and a Review of Pediatric Cases From the Literature.","authors":"Rai-Hseng Hsu, Wuh-Liang Hwu, Feng-Jung Yang, Ni-Chung Lee, Yin-Hsiu Chien","doi":"10.1002/mgg3.70228","DOIUrl":"10.1002/mgg3.70228","url":null,"abstract":"Background: Severe hypertriglyceridemia (HTG) is rare in children and is often caused by monogenic disorders. However, autoimmune mechanisms, particularly antibodies against glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), have emerged as rare causes. Pediatric-onset GPIHBP1 autoantibody-related HTG remains poorly characterized.Methods: We evaluated two 3-year-old children with extreme HTG (triglyceride level > 3000 mg/dL). Whole-exome sequencing was performed to investigate monogenic etiologies. Autoimmune testing included antinuclear antibodies (ANAs) and anti-Sjögren's syndrome-related antigen A (SSA) antibodies, as well as an enzyme-linked immunosorbent assay (ELISA) for anti-GPIHBP1 antibodies. A clinical response to immunosuppressive therapy was assessed. A literature review of previously reported pediatric cases was conducted.Results: No pathogenic variants were identified by whole-exome sequencing. Both patients were positive for ANAs (1:320, speckled), and one had high-titer anti-SSA antibodies. The ELISA confirmed the presence of anti-GPIHBP1 antibodies in both cases. Immunosuppressive therapy with hydroxychloroquine effectively reduced the triglyceride level in one patient, while the other required additional prednisolone. At follow-ups (ages 9 and 10), neither patient developed overt systemic autoimmune disease. A literature review revealed 13 previously reported pediatric cases, most of which were diagnosed after the age of 11 years and were frequently associated with systemic lupus erythematosus or other autoimmune disorders.Conclusion: GPIHBP1 autoantibody-related HTG is important and potentially treatable severe pediatric HTG, representing an early manifestation of autoimmune dysregulation that requires an accurate diagnosis and longitudinal surveillance.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"14 5","pages":"e70228"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical and Neurodevelopmental Course in a Case of EFNB1-Related Craniofrontonasal Syndrome With Unrepaired Craniosynostosis. efnb1相关颅额鼻综合征伴未修复颅缝闭塞1例的临床和神经发育过程。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2026-05-01 DOI: 10.1002/mgg3.70216

Dominique L Assing, Danielle E Jolly, Sarah Gluschitz, Beverly Nelson, Dong Li, Elizabeth J Bhoj, Tomoki T Nomakuchi, Andrew K Sobering

{"title":"Clinical and Neurodevelopmental Course in a Case of EFNB1-Related Craniofrontonasal Syndrome With Unrepaired Craniosynostosis.","authors":"Dominique L Assing, Danielle E Jolly, Sarah Gluschitz, Beverly Nelson, Dong Li, Elizabeth J Bhoj, Tomoki T Nomakuchi, Andrew K Sobering","doi":"10.1002/mgg3.70216","DOIUrl":"10.1002/mgg3.70216","url":null,"abstract":"Introduction: Craniofrontonasal syndrome displays an unusual X-linked dominant inheritance pattern due to pathogenic variants in EFNB1, which encodes a membrane-bound ligand for the ephrin receptor. Females exhibit a more severe phenotype than males and can have craniosynostosis, hypertelorism, craniofacial asymmetry, thoracic skeleton abnormalities, and an assortment of other features. Males typically only develop a milder hypertelorism, or they have no discernable features at all.Methods: Exome sequencing was used to identify a likely pathogenic EFNB1 c.129-2A>G splice site variant in an individual who had facial dysmorphology.Results: We describe a 14-year-old female from an underserved Caribbean population who had facial dysmorphology, microcephaly, and mild intellectual disability. She also had an uncorrected craniosynostosis that was diagnosed during clinical examination.Conclusion: The craniofrontonasal syndrome in the individual presented in this report is explained by the EFNB1 variant. The affected individual did not have surgical correction of her craniosynostosis, which might have contributed to her development of microcephaly and mild intellectual disability.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"14 5","pages":"e70216"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13106889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel LAMA1 Mutations in a Pedigree With Poretti-Boltshauser Syndrome: Implications for Hypomyelination. Poretti-Boltshauser综合征家系中新的LAMA1突变：对髓鞘生成低下的影响。

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2026-05-01 DOI: 10.1002/mgg3.70225

Si Huang, Yiyang Li, Jing Xin, Wenhui Mo, Xiuwen Lin, Bingbin Mai, Junbin He, Xiaoli Zhong, Jiaxin Xu

{"title":"Novel LAMA1 Mutations in a Pedigree With Poretti-Boltshauser Syndrome: Implications for Hypomyelination.","authors":"Si Huang, Yiyang Li, Jing Xin, Wenhui Mo, Xiuwen Lin, Bingbin Mai, Junbin He, Xiaoli Zhong, Jiaxin Xu","doi":"10.1002/mgg3.70225","DOIUrl":"10.1002/mgg3.70225","url":null,"abstract":"Background: Poretti-Boltshauser syndrome (PBS) is an autosomal recessive disorder caused by biallelic pathogenic variants in the LAMA1 gene, typically presenting with cerebellar dysplasia and fourth ventricle abnormalities. While neurological and ocular manifestations are well recognized, an association between LAMA1 variants and central nervous system (CNS) dysmyelination has not been previously established, and the underlying mechanisms remain unexplored.Case presentation: We report two pediatric siblings from a single family with novel compound heterozygous LAMA1 variants [c.505C>T (p.Arg169Ter) and c.634del (p.Ser212HisfsTer28)]. Both patients presented with classic PBS features including ataxia, developmental delay, and oculomotor apraxia. Neuroimaging confirmed cerebellar dysplasia and fourth ventricle abnormalities. Notably, we observed the unexpected concurrence of cerebral white matter hypomyelination, a finding rarely associated with PBS.Conclusions: This report presents the first clinical evidence linking novel LAMA1 variants to cerebral hypomyelination in PBS, based on the concordant observation in two affected siblings from the same family. Its specific association with LAMA1-related PBS had not been clearly delineated previously. Drawing on insights from the literature, we hypothesize that LAMA1 dysfunction may disrupt key stages of oligodendrocyte precursor cell biology, specifically survival, proliferation, migration, and differentiation, providing a potential mechanistic basis for the CNS hypomyelination observed in our patients. These findings expand both the phenotypic and genotypic spectrum associated with LAMA1 mutations and offer new insights into possible mechanisms of CNS hypomyelination in PBS.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"14 5","pages":"e70225"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Homozygous Pathogenic Variant in Elongation Factor-Like 1 (EFL1) as a Causal Factor in Shwachman-Diamond Syndrome 2 in a Palestinian Child, With Distinct Ocular Manifestations. 延伸因子样1 （EFL1）纯合子致病变异是巴勒斯坦儿童具有明显眼部表现的Shwachman-Diamond综合征2的致病因素

IF 1.6 4区医学

Molecular Genetics & Genomic Medicine Pub Date : 2026-05-01 DOI: 10.1002/mgg3.70226

Ibrahim Taha, Antonella Minelli, Cesare Danesino, Abdelrahman Swalmeh, Khalil Huraibat, Liana Al-Labadi, Rema Obar, Khaled R Beshtawi, Lubna Abu Samrah, Yousef Awlad Mohammad, Aya Farah, Abdulrahman Obar, Mutasem Khalaf, Orwa Nasser

{"title":"Homozygous Pathogenic Variant in Elongation Factor-Like 1 (EFL1) as a Causal Factor in Shwachman-Diamond Syndrome 2 in a Palestinian Child, With Distinct Ocular Manifestations.","authors":"Ibrahim Taha, Antonella Minelli, Cesare Danesino, Abdelrahman Swalmeh, Khalil Huraibat, Liana Al-Labadi, Rema Obar, Khaled R Beshtawi, Lubna Abu Samrah, Yousef Awlad Mohammad, Aya Farah, Abdulrahman Obar, Mutasem Khalaf, Orwa Nasser","doi":"10.1002/mgg3.70226","DOIUrl":"10.1002/mgg3.70226","url":null,"abstract":"Background: Shwachman-Diamond syndrome type 2 (SDS2) is a rare ribosomopathy caused by biallelic mutations in the EFL1 gene. This condition presents with features similar to classic SDS1 such as pancreatic insufficiency and haematologic abnormalities.Case presentation: We report a Palestinian female infant admitted to the NICU at H-Clinic Hospital, Ramallah, in January 2023, with a homozygous mutation in the EFL1 gene (c.3284G>A; p.Arg1095Gln), identified through whole exome sequencing and confirmed by Sanger sequencing. In addition to typical SDS2 features-pancytopenia, pancreatic insufficiency and growth failure-the patient exhibited unique manifestations, including ROP-like retinal changes, infantile esotropia with inferior oblique overaction, and elevated ACTH and 17-hydroxyprogesterone levels, indicating adrenal dysfunction.Findings: These findings expand the SDS2 phenotype to include novel ocular and endocrine involvement. No other pathogenic variants were identified by bioinformatic analysis. The recurrence of this variant in unrelated Palestinian families suggests a possible founder effect.Conclusion: This case underscores the importance of extended genetic testing and multidisciplinary evaluation in rare syndromes. It highlights the need for broader awareness of SDS2 among endocrinologists and ophthalmologists due to the novel clinical manifestations observed.","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"14 5","pages":"e70226"},"PeriodicalIF":1.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0