Journal of Advances in Medical and Biomedical Research

en Identification of a Pathogenic Mutation in GMPPB Gene Through Whole Exome Sequencing in Two Consanguineous Families with Limb-Girdle Muscular Dystrophy Medical Biology Medical Biology مقاله پژوهشی Original Research Article Background & Objective: Dystroglycanopathies represent heterogeneous clinical and genetic disorders typically characterized by weakness of the limb muscle. Pathogenic mutations in the GMPPB gene (OMIM # 615320) 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 LGMD2T.   Materials & Methods:  Two families with affected children diagnosed with LGMD2T 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_021971.4, c.308C>T (p. Pro103Leu) that entirely segregated from the observed phenotypes within his family. This variant was not identified in either the Exome Aggregation Consortium or the 1000 Genomes Project.  Conclusion: The present findings contribute to the expansion of genetic data for Iranian individuals affected by LGMD2T. This data can be instrumental in enhancing screening, diagnosis, and interpretation within families with a history of this disease.   Dystroglycanopathy, Guanosine diphosphate-mannose pyrophosphorylase-B coding, Limb-girdle muscular dystrophy, Muscular Dystrophies, Whole exome sequencing 269 279 http://journal.zums.ac.ir/browse.php?a_code=A-10-6910-1&slc_lang=en&sid=1 Mandana Rastegar rastegar.mandana@gmail.com 5200319475328460086678 5200319475328460086678 No Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran Maryam Moosavi maryam_moossavi@yahoo.com 5200319475328460086679 5200319475328460086679 No Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States Aazam Ahmadi Shadmehri Ahmadi.aazam@yahoo.com 5200319475328460086680 5200319475328460086680 No Social Welfare Organization of South Khorasan Province, Birjand, Iran Mohammad Dehghani Firoozabadi mdehghan@bums.ac.ir 5200319475328460086681 5200319475328460086681 No Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran Zahra Sorosh Zahrasorosh.zs@gmail.com 5200319475328460086682 5200319475328460086682 No Department of Family and Community Medicine, Birjand University of Medical Sciences, Birjand, Iran Hossein Dehghani 5200319475328460086683 5200319475328460086683 Yes Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran