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Basic and Clinical Neuroscience، جلد ۱۵، شماره ۶، صفحات ۰-۰
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| عنوان فارسی |
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| چکیده فارسی مقاله |
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| کلیدواژههای فارسی مقاله |
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| عنوان انگلیسی |
The Homozygous Pathogenic CAPN3 Variant Identified Using Whole-Exome Sequencing in Iranian Family with Limb-Girdle Muscular Dystrophy Recessive 1 |
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| چکیده انگلیسی مقاله |
Objective: Limb-girdle muscular dystrophies (LGMDs) are a diverse set of muscle disorders with several subgroups classified by defective genes and inheritance patterns. Numerous pathogenic mutations in calpain-3, the intracellular calcium-dependent protease encoded by the calcium-activated neutral proteinase 3 (CAPN3) gene, have been linked to an autosomal recessive type of this muscle disorder (LGMD2A), resulting in a weakened pelvic and shoulder girdle. This study aimed to investigate causative mutations in a consanguineous family with two afflicted offspring who were highly suspected of having LGMD.
Materials and Methods: This study sought to find causal variations in a consanguineous family with two affected offspring strongly suspected of LGMD referred to our Genetic Department at Ahvaz Noorgene Genetic and Clinical Laboratory to diagnose their muscular dystrophy type. We applied whole-exome sequencing to find the causal variations in the proband's genomic DNA. Then, we sought confirmation and performed a co-segregation analysis of the discovered variant with the phenotype in the proband and family members using Sanger sequencing.
Results: Following bioinformatic analysis and data filtering, we identified a homozygous variation, NM_000070.3:c.661G>T:p.G221C, within the CAPN3 gene that was validated by Sanger sequencing in the proband and segregated with LGMD2A in the family. The single alternation was described as pathogenic and regarded as a missense variant that altered protein features due to replacing the highly conserved amino acid glycine in the catalytic domain of calpain-3 protein with a cysteine.
Conclusion: The results of this investigation offer additional support for the genetic heterogeneity of LGMD and expand the mutational gene spectrum of CAPN3-associated muscular dystrophy by finding a pathogenic CAPN3 variant in both homozygous and heterozygous forms that had not previously been reported in these patients. |
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| کلیدواژههای انگلیسی مقاله |
Limb-girdle muscular dystrophy type 2A, Whole-exome sequencing, Calpain-3, Missense variant |
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| نویسندگان مقاله |
| Amin Sakhaei
Department of Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.
| Mitra Salehi
Department of Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.
| Javad Mohammadi-Asl
Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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| نشانی اینترنتی |
http://bcn.iums.ac.ir/browse.php?a_code=A-10-5978-1&slc_lang=en&sid=1 |
| فایل مقاله |
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| کد مقاله (doi) |
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| زبان مقاله منتشر شده |
en |
| موضوعات مقاله منتشر شده |
Cellular and molecular Neuroscience |
| نوع مقاله منتشر شده |
Original |
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