Identification of a Pathogenic Mutation in GMPPB Gene Through Whole Exome Sequencing in Two Consanguineous Families with Limb-Girdle Muscular Dystrophy

  • سال انتشار: 1403
  • محل انتشار: مجله علمی پژوهشی دانشگاه علوم پزشکی زنجان، دوره: 32، شماره: 153
  • کد COI اختصاصی: JR_ZUMS-32-153_005
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 71
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نویسندگان

Hossein Dehghani

Department of Family and Community Medicine, Birjand University of Medical Sciences, Birjand, Iran

mandana rastegar

Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran

Maryam Moossavi

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States

Aazam Ahmadi Shadmehri

Social Welfare Organization of South Khorasan Province, Birjand, Iran

Mohammad Dehghani Firoozabadi

Department of Neurology, Birjand University of Medical Sciences, Birjand, Iran

Zahra Sorosh

Department of Family and Community Medicine, Birjand University of Medical Sciences, Birjand, Iran

چکیده

Background & Objective: Dystroglycanopathies represent heterogeneous clinical and genetic disorders typically characterized by weakness of the limb muscle. Pathogenic mutations in the GMPPB gene (OMIM # ۶۱۵۳۲۰) have been identified in various syndromes, including CMD, LGMD, and CMS. In this present study, our aim is to elucidate the presence of pathogenic mutation in two consanguineous Iranian families affected by LGMD۲T.   Materials & Methods:  Two families with affected children diagnosed with LGMD۲T were recruited in the study. Comprehensive clinical examinations were performed by an expert neurologist on the proband and their respective families. Whole-exome sequencing (WES) was performed on genomic DNA extracted from peripheral blood mononuclear cells. Subsequently, candidate variants were identified using a bioinformatics pipeline, and familial co-segregation was confirmed through sanger sequencing. Results: The present study is focused on two families whose identified variants are confirmed. Our findings revealed a heterozygous missense mutation in the GMPPB gene (NM_۰۲۱۹۷۱.۴, c.۳۰۸C> T (p. Pro۱۰۳Leu) that entirely segregated from the observed phenotypes within his family. This variant was not identified in either the Exome Aggregation Consortium or the ۱۰۰۰ Genomes Project.  Conclusion: The present findings contribute to the expansion of genetic data for Iranian individuals affected by LGMD۲T. This data can be instrumental in enhancing screening, diagnosis, and interpretation within families with a history of this disease.

کلیدواژه ها

Dystroglycanopathy, Guanosine diphosphate-mannose pyrophosphorylase-B coding, Limb-girdle muscular dystrophy, Muscular Dystrophies, Whole exome sequencing

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