Molecular Genetic Analysis of Limb Girdle Muscular Dystrophy 2A (LGMD2A) in two consanguineous Pakistani families
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Khan, M. (2016). Molecular Genetic Analysis of Limb Girdle Muscular Dystrophy 2A (LGMD2A) in two consanguineous Pakistani families. KHYBER MEDICAL UNIVERSITY JOURNAL, 7(4), 156. Retrieved from https://www.kmuj.kmu.edu.pk/article/view/152

Abstract

Objectives: To investigate molecular pathogenesis of the disease and to significantly improve diagnosis and understanding of muscular dystrophy in Pakistani population.

Methods: This study was carried out at the department of Biochemistry, Quaid-I-Azam University Islamabad on two families affected with limb girdle muscular dystrophies (LGMD). Duration of the study was one year. Blood samples were collected from three normal and three affected individuals of the family A, eight affected individuals and four normal individuals of the family B for genetic analysis. Technique of homozygosity mapping was used to track the gene responsible for autosomal recessive LGMD2A in two families. The gene CAPN3 was sequenced in two families using Sanger sequencing approach.

Results: Genotyping data and haplotypes analysis showed that all affected individuals of family A (V-4, V-6, V-7) and family B (IV-1, IV-2, IV-4, IV-5, IV-6, IV-7, IV-10, IV-11) were homozygous while all normal individuals of family A (III-1, IV-1, V-5) and family B (III-4, III-5, IV-8, IV-12) were heterozygous, thus establishing linkage of the family A to CAPN3 gene on chromosome 15q15.1-q21.1. Subsequently, sequencing of all the 24 exons and exon-introns boundaries of CAPN3 genes showed no disease causing DNA sequence variant.

Conclusion: No disease causing DNA sequence variant was found in these exons suggesting the presence of mutation in the regulatory sequences or any other genes present in this region.

Key words: Cytogenetic Analysis (MeSH), Limb-girdle muscular dystrophy type 2A (MeSH), LGMD2A (MeSH), Consanguinity (MeSH), Pakistan (MeSH)

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References

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