Molecular Genetics & Genomic Medicine最新文献

{"title":"RHOBTB2 Variant p.Arg511Gln Causes Developmental and Epileptic Encephalopathy Type 64 in an Infant: A Case Report and Hotspot Variant Analysis.","authors":"Qian Liu, Feifei Li, Qin Ruan, Nana Wang, Zhengjun Fan","doi":"10.1002/mgg3.70059","DOIUrl":"10.1002/mgg3.70059","url":null,"abstract":"<p><strong>Background: </strong>Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of brain disorders. Variants in the Rho-related BTB domain-containing 2 gene (RHOBTB2) can lead to DEE64, which is characterized by early-onset epilepsy, varying degrees of motor developmental delay and intellectual disability, microcephaly, and movement disorders. More than half of the variants are located at Arg483 and Arg511 within the BTB domain; however, the underlying mechanism of action of these hotspot variants remains unexplored.</p><p><strong>Methods: </strong>We performed whole-exome and Sanger sequencing on the patient and his parents. We collected recurrent variant information from the literature on RHOBTB2 variants. We used Discovery Studio software to analyze the folding free energy of variant proteins, and the AlphaFold database to analyze structural alterations in mutant proteins.</p><p><strong>Results: </strong>The patient presented with early-onset epilepsy, developmental delay, and brain structural abnormalities. Genetic analysis revealed a de novo variant in RHOBTB2, c.1532G>A, p.(Arg511Gln). To date, 60 cases of DEE patients with RHOBTB2 variants have been reported, with approximately 50% of variants located at Arg483 and Arg511. Among them, p.Arg511Gln, p.Arg483His, and p.Arg511Trp have an incidence rate exceeding 10%. The folding free energy of these high-frequency variants proteins is reduced, which may lead to increased structural stability.</p><p><strong>Conclusion: </strong>This study highlights the importance of RHOBTB2 hotspot variants in DEE64 and provides insights into their potential mechanisms of action. We recommend RHOBTB2 gene testing for patients with relevant clinical manifestations to facilitate precise diagnosis and treatment of DEE.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 1","pages":"e70059"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059779","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}

{"title":"A De Novo Frameshift Variant in SMC1A Causes Non-Classic Cornelia de Lange Syndrome With Epilepsy: A Case Report and Literature Review.","authors":"Ying Yang, Liqing Chen, Zhenzhen Wang, Yaling Ding, Yan Liu","doi":"10.1002/mgg3.70058","DOIUrl":"10.1002/mgg3.70058","url":null,"abstract":"<p><strong>Background: </strong>Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder. Although individuals with variants in the SMC1A gene are less commonly seen in CdLS, they exhibit a high incidence of epilepsy and atypical phenotypic variability.</p><p><strong>Methods: </strong>The clinical data of a patient with non-classic CdLS and epilepsy caused by an SMC1A variant were summarized. A literature review was conducted to analyze the genotype-phenotype correlations and epilepsy characteristics in related cases.</p><p><strong>Results: </strong>A 5-year-6-month-old female patient presented with facial features, double outlet right ventricle (DORV), and recurrent epilepsy. Whole exome sequencing (WES) identified a de novo heterozygous frameshift mutation, c.2890_2893del (p.Ser964Valfs*26), in the SMC1A gene. A review of the literature identified several characteristics of non-classic CdLS with epilepsy caused by SMC1A variants: the majority of cases were non-classic (81.5%), predominantly female (68.2%), with a median onset age of 11.5 months. Common features included severe/profound developmental delay (52.6%), hypotonia (18.2%), cardiovascular anomalies (36.4%), and intrauterine growth retardation (IUGR) (22.7%). Among the non-classic cases, seizure clusters occurred in 22.7%, status epilepticus in 18.2%, and drug-resistant epilepsy in 33.3%. Genotypes in non-classic cases included missense mutations (40.9%), frameshift mutations (31.8%), splice site variants (9.1%), nonsense mutations (9.1%), deletions (4.5%), and truncations (4.5%).</p><p><strong>Conclusion: </strong>Our study expanded the phenotypic data and mutational spectrum of non-classic CdLS with epilepsy caused by SMC1A variants. Compared to individuals with the classic form of CdLS, the non-classic cases appeared more frequently in females and were associated with a higher prevalence of severe/profound developmental delay and cardiovascular anomalies. In contrast, IUGR was significantly less common in non-classic individuals. Regarding epilepsy characteristics, some individuals including seizure clusters, status epilepticus, drug resistance, and hypotonia, no significant differences were observed between classic and non-classic cases. The predominant genotypes in non-classic cases were missense and frameshift mutations.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"13 1","pages":"e70058"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008519","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}

{"title":"Homozygous Microdeletion Involving Exon 1 of ERCC8 and NDUFAF2 With Uniparental Isodisomy of Chromosome 5.","authors":"Kaori Yamoto, Kosuke Yamada, Kenji Shimizu, Sachiko Miyamoto, Mitsuko Nakashima, Hirotomo Saitsu","doi":"10.1002/mgg3.70037","DOIUrl":"10.1002/mgg3.70037","url":null,"abstract":"<p><strong>Background: </strong>Uniparental isodisomy (UPiD) refers to a condition, in which both homologous chromosomes are inherited from only one parental homolog, which can result in either imprinting disorders or autosomal recessive conditions.</p><p><strong>Methods: </strong>We performed chromosomal microarray analysis, exome sequencing (ES), and RNA sequencing (RNA-seq) using the patient's urine-derived cells on a patient with growth retardation and multiple congenital anomalies.</p><p><strong>Results: </strong>We identified a homozygous ~0.53 kb microdeletion at 5q12.1, which was transmitted from the father with paternal UPiD(5). The deletion encompassed the first exon of both the ERCC8 and NDUFAF2 genes, which are responsible for Cockayne syndrome (CS) and mitochondrial complex I deficiency, respectively. Furthermore, RNA-seq confirmed the reduced expression of both genes. Indeed, in addition to clinical features common to both syndromes, such as growth retardation, developmental delay, and feeding difficulties, the patient exhibited blended phenotypes: the characteristic features of CS, including arthrogryposis, microcephaly, and facial dysmorphisms, and those of mitochondrial complex I deficiency, including high serum lactate levels and lethal apnea resulting in a severe clinical course.</p><p><strong>Conclusion: </strong>The results imply that ES in combination with RNA-seq could be a powerful method for the detection of underlying factors responsible for rare genetic conditions, such as UPD.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 12","pages":"e70037"},"PeriodicalIF":1.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770647","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}

{"title":"Screening of Inherited Retinal Disease Patients in a Low-Resource Setting Using an Augmented Next-Generation Sequencing Panel.","authors":"Nicole Midgley, George Rebello, Lara K Holtes, Raj Ramesar, Lisa Roberts","doi":"10.1002/mgg3.70046","DOIUrl":"10.1002/mgg3.70046","url":null,"abstract":"<p><strong>Background: </strong>Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders affecting millions worldwide. Despite the widespread adoption of next-generation sequencing (NGS) panels, there remains a critical gap in the genetically diverse and understudied African populations.</p><p><strong>Methods: </strong>One hundred and thirty-five South African patients affected by various IRDs underwent NGS using a custom-targeted panel sequencing over 100 known genes. The panel was supplemented by in silico screening for a MAK-Alu insertion and screening of seven functionally established deep intronic variants.</p><p><strong>Results: </strong>Through our combined screening strategy, we obtained a probable genetic diagnosis for 56% of the cohort. We identified 83 unique variants in 29 IRD genes underlying the disease, including 16 putative novel variants. Molecular findings prompted recommendations for clinical re-examination in ten patients. Resolution rates varied across clinical classifications and population groups.</p><p><strong>Conclusions: </strong>This study reports the first use of a targeted NGS panel for IRDs in southern Africa, demonstrating a cost-effective, customisable approach that optimises both diagnostic yield and resource efficiency, making it a valuable tool for IRD molecular characterisation in resource-limited settings. Augmenting the panel by screening for variants relevant to South African patients allowed us to achieve a resolution rate in line with international studies. Our study underscores the importance of investigating diverse populations to bridge disparities in genomic research and improve diagnostic outcomes for underrepresented population groups.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 12","pages":"e70046"},"PeriodicalIF":1.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829315","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}

{"title":"MiR-766-3p Inhibit the Proliferation, Stemness, and Cell Cycle of Pancreatic Cancer Cells Through the MAPK/ERK Signaling Pathway.","authors":"Zhipeng Quan, Ziwei Yin, Yuelin Huang, Xuemei Huang, Hao Huang, Qingrong Mo, Jianhua Gong, Lingyun Liu, Yi Zhou, Yaqun Yu","doi":"10.1002/mgg3.70049","DOIUrl":"10.1002/mgg3.70049","url":null,"abstract":"<p><strong>Background: </strong>As a commonly identified cancer in clinics, pancreatic cancer (PC) has poor prognostic outcomes. This work focused on clarifying the association between MIR-766-3P expression and PC development and progression, as well as the possible role as a biomarker in PC.</p><p><strong>Methods: </strong>MIR-766-3P expression within the human PC cells and samples was measured through miRNA RT-PCR. The gene levels regulated by MIR-766-3P were analyzed through western blot (WB) and qRT-PCR. To analyze whether MIR-766-3P was of certain significance in in vitro and in vivo PC cell proliferation, stemness, and cell cycle progression, the gain/loss-of-function assays were performed. Bioinformatics, RNA sequencing (RNA-seq), and luciferase reporter assay were conducted for exploring regulatory role of MIR-766-3P/MAPK1/MAPK/ERK signal axis in PC.</p><p><strong>Result: </strong>In comparison with the normal controls, MIR-766-3P expression markedly decreased the tissues and cells of PC. Furthermore, MIR-766-3P could remarkably inhibit the proliferation, stemness, cell cycle progression, and development of PC. The analyses using RNA-seq, and dual-luciferase examination showed that MIR-766-3P could directly target mitogen-activated protein kinase 1 (MAPK1). According to Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, MIR-766-3P could affect PC malignant phenotype by MAPK1 and the regulation of the MAPK/ERK-related pathway.</p><p><strong>Conclusion: </strong>MIR-766-3P has a certain impact on PC malignant phenotype through combining with MAPK1 while regulating MAPK/ERK-related pathway in vitro and in vivo.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 12","pages":"e70049"},"PeriodicalIF":1.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847039","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}

{"title":"A Novel Mutation Located in the N-Terminal Domain of MYO15A Caused Sensorineural Hearing Loss.","authors":"Yanli Wang, Zengping Liu, Yong Li, Zhipeng Nie, Baicheng Xu, Yiming Zhu, Shihong Duan, Xingjian Chen, Huan Tan, Jiong Dang, Minxin Guan, Yufen Guo","doi":"10.1002/mgg3.70042","DOIUrl":"10.1002/mgg3.70042","url":null,"abstract":"<p><strong>Background: </strong>MYO15A is one of the common genes of severe-to-profound sensorineural deafness. Mutations in this gene can cause both pre- and post-lingual hearing losses. In this study, a novel MYO15A variant (c.2482C>T) was identified to be associated with autosomal recessive non-syndromic hearing loss (ARNSHL) in a Chinese Uighur family.</p><p><strong>Methods: </strong>To examine the effects of the MYO15A mutation on the morphology and function of the derived hair cell-like cells, two iPSCs were generated separately from the proband and a mutation-negative family member and those were then induced to hair cell-like cells.</p><p><strong>Results: </strong>Results showed that this homozygous MYO15A mutation (PVS1 + PM2 + PP1 + PP3), which is located in the N-terminal domain, displayed significant differences in the morphology and function of hair cell-like cells between the proband and the normal control, although it had no effect on the totipotency of iPSCs.</p><p><strong>Conclusion: </strong>Our study demonstrates that the novel variant c.2482C>T in the MYO15A gene may cause inner ear hair cell dysfunction and audiological disorders in this family.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 12","pages":"e70042"},"PeriodicalIF":1.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770575","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}

{"title":"Genotype-Phenotype Spectrum of 52 Mexican Patients With Fabry Disease: A Novel GLA Variant With Atypical Phenotype.","authors":"Tamara N Kimball, Pamela Rivero-García, Eduardo R Argaiz, Jorge Eduardo Gaytan-Arocha, Norma Ofelia Uribe Uribe, Juan José Morales Suárez","doi":"10.1002/mgg3.70039","DOIUrl":"https://doi.org/10.1002/mgg3.70039","url":null,"abstract":"<p><strong>Introduction: </strong>Fabry disease (FD) is a rare lysosomal type 3 disorder with an X-linked inheritance pattern caused by pathogenic variants in the GLA gene. This study aimed to describe the genotype and phenotype of 52 Mexican patients with FD.</p><p><strong>Methods: </strong>We included 12 patients with clinical and molecular diagnosis of FD treated at our institution and 40 FD Mexican patients already reported in the literature.</p><p><strong>Results: </strong>The most frequent manifestations were acroparesthesias (71.2%), hypohidrosis or anhidrosis (48.1%), heat intolerance (46.2%), and proteinuria (42.3%). Renal and neurological manifestations were more prevalent in males than females. Cardiac involvement included hypertrophic cardiomyopathy and Wolf-Parkinson-White arrhythmia. Cornea verticillata was seen in 14 patients (26.9%) and angiokeratomas in 15 (28.8%). We identified 14 variants in the GLA gene in Mexican patients with FD. We found a novel variant GLA c.122C>G that causes an atypical FD phenotype with predominantly neurological involvement in two unrelated patients, one of them with a forthright clinical and radiological overlap of Multiple Sclerosis and normal biological biomarkers, thus requiring a renal biopsy that helped confirm the diagnosis of FD.</p><p><strong>Conclusions: </strong>The genotype and phenotype of Mexican patients with FD are similar to other populations. Atypical phenotype of FD, such as the one associated with the novel variant c.122C>G, can be a diagnostic challenge, as it can be mixed up with MS. Our findings confirm the limitations of noninvasive diagnostic methods and the necessity of the renal biopsy when the clinical suspicion of FD is high.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 12","pages":"e70039"},"PeriodicalIF":1.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770592","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}

{"title":"A Novel Homozygote Pathogenic Variant in the DIAPH1 Gene Associated With Seizures, Cortical Blindness, and Microcephaly Syndrome (SCBMS): Report of a Family and Literature Review.","authors":"Emran Esmaeilzadeh, Sajjad Biglari, Meysam Mosallaei, Hamid Reza Khorram Khorshid, Hassan Vahidnezhad, Mohammad Amin Tabatabaiefar","doi":"10.1002/mgg3.70031","DOIUrl":"10.1002/mgg3.70031","url":null,"abstract":"<p><strong>Objective: </strong>Mammalian Diaphanous-Related Formin (mDia1), which is encoded by the DIAPH1 gene, serves as essential for the regulation of cell morphology and cytoskeletal organization. The role of DIAPH1 in brain development has been extensively established. This study aims to evaluate the clinical, neuroradiological, and genetic characteristics of patients with DIAPH1-related disease and determine probable genotype-phenotype relationships.</p><p><strong>Methods: </strong>In the current study, exome sequencing was performed to identify the genetic basis of the clinical presentation in an Iranian 7-year-old boy. Validation of the detected variant was done by Sanger sequencing. Furthermore, we performed a comprehensive review of the literature.</p><p><strong>Results: </strong>Here, we detected a novel homozygous c.1285C> T (p.Gln429*) pathogenic variant in the patient. In silico analysis with prediction software tools identified this variant as a probable source of damage. Twenty cases from seven studies were found after a review of the literature. The patients' main symptoms were a developmental delay, microcephaly, and seizures. The mean age of onset for patients in the group of 20 patients with a known age of onset was 2.3 months (SD = 1.6). Of the variants identified, c.2769del, c.684+1G>A, and c.2332C> T were identified in 72% of the patients.</p><p><strong>Conclusion: </strong>Considering the variant's position in the gene and the encoding protein, a pathogenic effect is predicted for the variant. So, the patient's clinical manifestation is probably caused by this pathogenic variant. Moreover, by studying clinical manifestations in all molecularly confirmed reported cases, provided a comprehensive overview of clinical presentation, and attempted to find a genotype-phenotype correlation.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70031"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693294","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}

{"title":"SRY+ Derivative X Chromosome in a Female With Apparently Typical Sexual Development.","authors":"Casey J Brewer, Alyxis G Coyan, Nicki Smith, Brittany Jones, Teresa A Smolarek, Jie Liu","doi":"10.1002/mgg3.70033","DOIUrl":"10.1002/mgg3.70033","url":null,"abstract":"<p><strong>Background: </strong>When the SRY gene is present in a 46,XX fetus, some degree of testicular development is expected. Our laboratory performed prenatal genetic testing for a fetus that had screened positive for Y chromosome material by noninvasive prenatal screening (NIPS) but that had apparently typical female development by ultrasound imaging. The aim of this study was to determine the clinical relevance of the NIPS results.</p><p><strong>Methods: </strong>We analyzed fetal material obtained via amniocentesis procedure by G-banding, microarray, and fluorescence in situ hybridization (FISH). Optical genome mapping (OGM) was also performed.</p><p><strong>Results: </strong>G-band analysis revealed a normal 46,XX karyotype. Microarray and FISH analyses together detected an SRY+ gain of 5.7 Mb from terminal Yp that was translocated to terminal Xq, with a loss of 1.6 Mb from terminal Xq. The final karyotype was 46,X,der(X)t(X;Y)(q28;p11.2). Prenatal ultrasound and postnatal physical examination revealed apparently typical female genitalia. The Xq deletion encompassed a gene, IKBKG, that is sensitive to loss of function, suggesting that preferential inactivation of the derivative X chromosome allowed for typical female development. OGM software did not directly identify this translocation.</p><p><strong>Conclusion: </strong>This case demonstrates how the SRY gene may be present in a 46,XX biological female without differences of sexual development.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e70033"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624276","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}

{"title":"In a cohort of 961 clinically suspected Duchenne muscular dystrophy patients, 105 were diagnosed to have other muscular dystrophies (OMDs), with LGMD2E (variant SGCB c.544A>C) being the most common.","authors":"Priya Karthikeyan, Shalini H Kumar, Arati Khanna-Gupta, Lakshmi Bremadesam Raman","doi":"10.1002/mgg3.2123","DOIUrl":"10.1002/mgg3.2123","url":null,"abstract":"<p><strong>Background: </strong>Targeted next generation sequence analyses in a cohort of 961 previously described patients with clinically suspected Duchene muscular dystrophy (DMD) revealed that 145/961 (15%) had variants in genes associated with other muscular dystrophies (OMDs).</p><p><strong>Methods: </strong>NGS was carried out in DMD negative patients after deletion/duplication analysis followed by WES for No variant cases.</p><p><strong>Results: </strong>The majority of patients with OMDs had autosomal recessive diseases that included Limb-Girdle Muscular Dystrophies (LGMDs), Bethlem, Ullrich congenital Myopathies and Emery-Driefuss muscular dystrophy. 3.5% of patients were identified with other disorders like Charcot-Marie Tooth and Nemaline myopathy. A small percentage of patients, 0.6% remain undiagnosed. Of a total of 78 genetic variants identified, 44 were found to be novel. Interestingly, a third of patients with OMDs were found to have LGMD2E/R4, a severe form of LGMD that afflicts young children with clinical symptoms similar to DMD. Almost one third of the unrelated LGMD2E/R4 patients had the same point mutation (c.544A>C) in the SGCB gene, suggestive of a founder effect, described here for the first time in India.</p><p><strong>Conclusion: </strong>This study underscores the need for a complete genetic work up to precisely diagnose patients and to initiate appropriate counseling programs, disease management and prevention strategies.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":"12 11","pages":"e2123"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644424","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}