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Volume 32, Issue 153 (July & August 2024)
J Adv Med Biomed Res 2024, 32(153): 269-279 |
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Rastegar M, Moosavi M, Ahmadi Shadmehri A, Dehghani Firoozabadi M, Sorosh Z, Dehghani H. Identification of a Pathogenic Mutation in GMPPB Gene Through Whole Exome Sequencing in Two Consanguineous Families with Limb-Girdle Muscular Dystrophy. J Adv Med Biomed Res 2024; 32 (153) :269-279
URL: http://journal.zums.ac.ir/article-1-7385-en.html
URL: http://journal.zums.ac.ir/article-1-7385-en.html
Mandana Rastegar1 
, Maryam Moosavi2 , Aazam Ahmadi Shadmehri3 , Mohammad Dehghani Firoozabadi1 , Zahra Sorosh4 , Hossein Dehghani *1
, Maryam Moosavi2 , Aazam Ahmadi Shadmehri3 , Mohammad Dehghani Firoozabadi1 , Zahra Sorosh4 , Hossein Dehghani *1
1- Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran
2- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States
3- Social Welfare Organization of South Khorasan Province, Birjand, Iran
4- Department of Family and Community Medicine, Birjand University of Medical Sciences, Birjand, Iran
2- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States
3- Social Welfare Organization of South Khorasan Province, Birjand, Iran
4- Department of Family and Community Medicine, Birjand University of Medical Sciences, Birjand, Iran
Abstract: (765 Views)
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.
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.
Keywords: Dystroglycanopathy, Guanosine diphosphate-mannose pyrophosphorylase-B coding, Limb-girdle muscular dystrophy, Muscular Dystrophies, Whole exome sequencing
Type of Study: Original Research Article |
Subject:
Medical Biology
Received: 2023/11/12 | Accepted: 2024/02/19 | Published: 2024/08/20
Received: 2023/11/12 | Accepted: 2024/02/19 | Published: 2024/08/20
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