Causative variants linked with limb girdle muscular dystrophy in an Iranian population: 6 novel variants
Abstract Background Limb‐girdle muscular dystrophy (LGMD) is a non‐syndromic muscular dystrophy caused by variations in the genes involved in muscle structure, function and repair. The heterogeneity in the severity, progression, age of onset, and causative genes makes next‐generation sequencing (NGS...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.2101 |
| _version_ | 1828012495480029184 |
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| author | Hamidreza Mianesaz Safoura Ghalamkari Mansoor Salehi Mahdiyeh Behnam Majid Hosseinzadeh Keivan Basiri Majid Ghasemi Maryam Sedghi Behnaz Ansari |
| author_facet | Hamidreza Mianesaz Safoura Ghalamkari Mansoor Salehi Mahdiyeh Behnam Majid Hosseinzadeh Keivan Basiri Majid Ghasemi Maryam Sedghi Behnaz Ansari |
| author_sort | Hamidreza Mianesaz |
| collection | DOAJ |
| description | Abstract Background Limb‐girdle muscular dystrophy (LGMD) is a non‐syndromic muscular dystrophy caused by variations in the genes involved in muscle structure, function and repair. The heterogeneity in the severity, progression, age of onset, and causative genes makes next‐generation sequencing (NGS) a necessary approach for the proper diagnosis of LGMD. Methods In this article, 26 Iranian patients with LGMD criteria were diagnosed with disease variants in the genes encoding calpain3, dysferlin, sarcoglycans and Laminin α‐2. Patients were referred to the hospital with variable distribution of muscle wasting and progressive weakness in the body. The symptoms along with biochemical and EMG tests were suggestive of LGMD; thus the genomic DNA of patients were investigated by whole‐exome sequencing including flanking intronic regions. The target genes were explored for the disease‐causing variants. Moreover, the consequence of the amino acid alterations on proteins' secondary structure and function was investigated for a better understanding of the pathogenicity of variants. Variants were sorted based on the genomic region, type and clinical significance. Results In a comprehensive investigation of previous clinical records, 6 variations were determined as novel, including c.1354–2 A > T and c.3169_3172dupCGGC in DYSF, c.568 G > T in SGCD, c.7243 C > T, c.8662_8663 insT and c. 4397G > C in LAMA2. Some of the detected variants were located in functional domains and/or near to the post‐translational modification sites, altering or removing highly conserved regions of amino acid sequence. |
| first_indexed | 2024-04-10T09:32:25Z |
| format | Article |
| id | doaj.art-d474172c545b4bdaa3846f360e4c73ba |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-10T09:32:25Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-d474172c545b4bdaa3846f360e4c73ba2023-02-18T19:05:42ZengWileyMolecular Genetics & Genomic Medicine2324-92692023-02-01112n/an/a10.1002/mgg3.2101Causative variants linked with limb girdle muscular dystrophy in an Iranian population: 6 novel variantsHamidreza Mianesaz0Safoura Ghalamkari1Mansoor Salehi2Mahdiyeh Behnam3Majid Hosseinzadeh4Keivan Basiri5Majid Ghasemi6Maryam Sedghi7Behnaz Ansari8Department of Human Genetics, Medical School University of Debrecen Debrecen HungaryDepartment of Genetics and Molecular Biology Isfahan University of Medical Sciences Isfahan IranDepartment of Genetics and Molecular Biology Isfahan University of Medical Sciences Isfahan IranCellular, Molecular and Genetics Research Center Isfahan University of Medical Sciences Isfahan IranDepartment of Genetics and Molecular Biology Isfahan University of Medical Sciences Isfahan IranMetabolic Disorders Research Center, Endocrinology and Metabolism Molecular‐Cellular Sciences Institute Tehran University of Medical Science Tehran IranMetabolic Disorders Research Center, Endocrinology and Metabolism Molecular‐Cellular Sciences Institute Tehran University of Medical Science Tehran IranMedical Genetics Laboratory, Alzahra University Hospital Isfahan University of Medical Sciences Isfahan IranDepartment of Neurology Isfahan University of Medical Sciences Isfahan IranAbstract Background Limb‐girdle muscular dystrophy (LGMD) is a non‐syndromic muscular dystrophy caused by variations in the genes involved in muscle structure, function and repair. The heterogeneity in the severity, progression, age of onset, and causative genes makes next‐generation sequencing (NGS) a necessary approach for the proper diagnosis of LGMD. Methods In this article, 26 Iranian patients with LGMD criteria were diagnosed with disease variants in the genes encoding calpain3, dysferlin, sarcoglycans and Laminin α‐2. Patients were referred to the hospital with variable distribution of muscle wasting and progressive weakness in the body. The symptoms along with biochemical and EMG tests were suggestive of LGMD; thus the genomic DNA of patients were investigated by whole‐exome sequencing including flanking intronic regions. The target genes were explored for the disease‐causing variants. Moreover, the consequence of the amino acid alterations on proteins' secondary structure and function was investigated for a better understanding of the pathogenicity of variants. Variants were sorted based on the genomic region, type and clinical significance. Results In a comprehensive investigation of previous clinical records, 6 variations were determined as novel, including c.1354–2 A > T and c.3169_3172dupCGGC in DYSF, c.568 G > T in SGCD, c.7243 C > T, c.8662_8663 insT and c. 4397G > C in LAMA2. Some of the detected variants were located in functional domains and/or near to the post‐translational modification sites, altering or removing highly conserved regions of amino acid sequence.https://doi.org/10.1002/mgg3.2101calpaindysferlinlamininLGMDlimb‐girdle muscular dystrophymuscular disorders |
| spellingShingle | Hamidreza Mianesaz Safoura Ghalamkari Mansoor Salehi Mahdiyeh Behnam Majid Hosseinzadeh Keivan Basiri Majid Ghasemi Maryam Sedghi Behnaz Ansari Causative variants linked with limb girdle muscular dystrophy in an Iranian population: 6 novel variants Molecular Genetics & Genomic Medicine calpain dysferlin laminin LGMD limb‐girdle muscular dystrophy muscular disorders |
| title | Causative variants linked with limb girdle muscular dystrophy in an Iranian population: 6 novel variants |
| title_full | Causative variants linked with limb girdle muscular dystrophy in an Iranian population: 6 novel variants |
| title_fullStr | Causative variants linked with limb girdle muscular dystrophy in an Iranian population: 6 novel variants |
| title_full_unstemmed | Causative variants linked with limb girdle muscular dystrophy in an Iranian population: 6 novel variants |
| title_short | Causative variants linked with limb girdle muscular dystrophy in an Iranian population: 6 novel variants |
| title_sort | causative variants linked with limb girdle muscular dystrophy in an iranian population 6 novel variants |
| topic | calpain dysferlin laminin LGMD limb‐girdle muscular dystrophy muscular disorders |
| url | https://doi.org/10.1002/mgg3.2101 |
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