Genetic Modifiers of Hereditary Neuromuscular Disorders and Cardiomyopathy
Novel genetic variants exist in patients with hereditary neuromuscular disorders (NMD), including muscular dystrophy. These patients also develop cardiac manifestations. However, the association between these gene variants and cardiac abnormalities is understudied. To determine genetic modifiers and...
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MDPI AG
2021-02-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/2/349 |
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| author | Sholeh Bazrafshan Hani Kushlaf Mashhood Kakroo John Quinlan Richard C. Becker Sakthivel Sadayappan |
| author_facet | Sholeh Bazrafshan Hani Kushlaf Mashhood Kakroo John Quinlan Richard C. Becker Sakthivel Sadayappan |
| author_sort | Sholeh Bazrafshan |
| collection | DOAJ |
| description | Novel genetic variants exist in patients with hereditary neuromuscular disorders (NMD), including muscular dystrophy. These patients also develop cardiac manifestations. However, the association between these gene variants and cardiac abnormalities is understudied. To determine genetic modifiers and features of cardiac disease in NMD patients, we have reviewed electronic medical records of 651 patients referred to the Muscular Dystrophy Association Care Center at the University of Cincinnati and characterized the clinical phenotype of 14 patients correlating with their next-generation sequencing data. The data were retrieved from the electronic medical records of the 14 patients included in the current study and comprised neurologic and cardiac phenotype and genetic reports which included comparative genomic hybridization array and NGS. Novel associations were uncovered in the following eight patients diagnosed with Limb-girdle Muscular Dystrophy, Bethlem Myopathy, Necrotizing Myopathy, Charcot-Marie-Tooth Disease, Peripheral Polyneuropathy, and Valosin-containing Protein-related Myopathy. Mutations in COL6A1, COL6A3, SGCA, SYNE1, FKTN, PLEKHG5, ANO5, and SMCHD1 genes were the most common, and the associated cardiac features included bundle branch blocks, ventricular chamber dilation, septal thickening, and increased outflow track gradients. Our observations suggest that features of cardiac disease and modifying gene mutations in patients with NMD require further investigation to better characterize genotype–phenotype relationships. |
| first_indexed | 2024-03-09T05:08:08Z |
| format | Article |
| id | doaj.art-7ab3130989b74c3ab83d8da0c43627a7 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T05:08:08Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7ab3130989b74c3ab83d8da0c43627a72023-12-03T12:52:38ZengMDPI AGCells2073-44092021-02-0110234910.3390/cells10020349Genetic Modifiers of Hereditary Neuromuscular Disorders and CardiomyopathySholeh Bazrafshan0Hani Kushlaf1Mashhood Kakroo2John Quinlan3Richard C. Becker4Sakthivel Sadayappan5Heart, Lung and Vascular Institute, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USADepartment of Neurology and Rehabilitation Medicine, Neuromuscular Center, University of Cincinnati Gardner Neuroscience Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USAHeart, Lung and Vascular Institute, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USADepartment of Neurology and Rehabilitation Medicine, Neuromuscular Center, University of Cincinnati Gardner Neuroscience Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USAHeart, Lung and Vascular Institute, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USAHeart, Lung and Vascular Institute, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USANovel genetic variants exist in patients with hereditary neuromuscular disorders (NMD), including muscular dystrophy. These patients also develop cardiac manifestations. However, the association between these gene variants and cardiac abnormalities is understudied. To determine genetic modifiers and features of cardiac disease in NMD patients, we have reviewed electronic medical records of 651 patients referred to the Muscular Dystrophy Association Care Center at the University of Cincinnati and characterized the clinical phenotype of 14 patients correlating with their next-generation sequencing data. The data were retrieved from the electronic medical records of the 14 patients included in the current study and comprised neurologic and cardiac phenotype and genetic reports which included comparative genomic hybridization array and NGS. Novel associations were uncovered in the following eight patients diagnosed with Limb-girdle Muscular Dystrophy, Bethlem Myopathy, Necrotizing Myopathy, Charcot-Marie-Tooth Disease, Peripheral Polyneuropathy, and Valosin-containing Protein-related Myopathy. Mutations in COL6A1, COL6A3, SGCA, SYNE1, FKTN, PLEKHG5, ANO5, and SMCHD1 genes were the most common, and the associated cardiac features included bundle branch blocks, ventricular chamber dilation, septal thickening, and increased outflow track gradients. Our observations suggest that features of cardiac disease and modifying gene mutations in patients with NMD require further investigation to better characterize genotype–phenotype relationships.https://www.mdpi.com/2073-4409/10/2/349neuromuscular disordersmuscular dystrophycardiomyopathygenotype–phenotype relationshipsnext-generation sequencing |
| spellingShingle | Sholeh Bazrafshan Hani Kushlaf Mashhood Kakroo John Quinlan Richard C. Becker Sakthivel Sadayappan Genetic Modifiers of Hereditary Neuromuscular Disorders and Cardiomyopathy Cells neuromuscular disorders muscular dystrophy cardiomyopathy genotype–phenotype relationships next-generation sequencing |
| title | Genetic Modifiers of Hereditary Neuromuscular Disorders and Cardiomyopathy |
| title_full | Genetic Modifiers of Hereditary Neuromuscular Disorders and Cardiomyopathy |
| title_fullStr | Genetic Modifiers of Hereditary Neuromuscular Disorders and Cardiomyopathy |
| title_full_unstemmed | Genetic Modifiers of Hereditary Neuromuscular Disorders and Cardiomyopathy |
| title_short | Genetic Modifiers of Hereditary Neuromuscular Disorders and Cardiomyopathy |
| title_sort | genetic modifiers of hereditary neuromuscular disorders and cardiomyopathy |
| topic | neuromuscular disorders muscular dystrophy cardiomyopathy genotype–phenotype relationships next-generation sequencing |
| url | https://www.mdpi.com/2073-4409/10/2/349 |
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