Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy
Background Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by mutations within the dystrophin gene. DMD is characterized by progressive skeletal muscle degeneration and atrophy and progressive cardiomyopathy. It has been observed the severity of cardiomyopathy varies in patients...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.120.016799 |
| _version_ | 1797607504274784256 |
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| author | Xuan Jiang Yanqiu Shao Faris G. Araj Alpesh A. Amin Benjamin M. Greenberg Mark H. Drazner Chao Xing Pradeep P. A. Mammen |
| author_facet | Xuan Jiang Yanqiu Shao Faris G. Araj Alpesh A. Amin Benjamin M. Greenberg Mark H. Drazner Chao Xing Pradeep P. A. Mammen |
| author_sort | Xuan Jiang |
| collection | DOAJ |
| description | Background Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by mutations within the dystrophin gene. DMD is characterized by progressive skeletal muscle degeneration and atrophy and progressive cardiomyopathy. It has been observed the severity of cardiomyopathy varies in patients with DMD. Methods and Results A cohort of male patients with DMD and female DMD carriers underwent whole exome sequencing. Potential risk factor variants were identified according to their functional annotations and frequencies. Cardiac function of 15 male patients with DMD was assessed by cardiac magnetic resonance imaging, and various cardiac magnetic resonance imaging parameters and circulating biomarkers were compared between genotype groups. Five subjects carrying potential risk factor variants in the cystic fibrosis transmembrane regulator gene demonstrated lower left ventricular ejection fraction, larger left ventricular end‐diastolic volume, and higher NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels compared with 10 subjects who did not carry the potential risk factor variants (P=0.023, 0.019 and 0.028, respectively). Conclusions This study revealed heterozygous cystic fibrosis transmembrane regulator gene missense variants were associated with worse cardiac function in patients with DMD. The cystic fibrosis transmembrane regulator gene may serve as a genetic modifier that accounts for more severe cardiomyopathy in patients with DMD, who would require more aggressive management of the cardiomyopathy. |
| first_indexed | 2024-03-11T05:30:51Z |
| format | Article |
| id | doaj.art-8aa8b168092a4349a5297712b3bc66fd |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-11T05:30:51Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-8aa8b168092a4349a5297712b3bc66fd2023-11-17T17:08:10ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802020-10-0191910.1161/JAHA.120.016799Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular DystrophyXuan Jiang0Yanqiu Shao1Faris G. Araj2Alpesh A. Amin3Benjamin M. Greenberg4Mark H. Drazner5Chao Xing6Pradeep P. A. Mammen7Department of Internal Medicine UT Southwestern Medical Center Dallas TXDepartment of Population & Data Sciences UT Southwestern Medical Center Dallas TXDepartment of Internal Medicine UT Southwestern Medical Center Dallas TXDepartment of Internal Medicine UT Southwestern Medical Center Dallas TXDepartment of Neurology & Neurotherapeutics UT Southwestern Medical Center Dallas TXDepartment of Internal Medicine UT Southwestern Medical Center Dallas TXDepartment of Population & Data Sciences UT Southwestern Medical Center Dallas TXDepartment of Internal Medicine UT Southwestern Medical Center Dallas TXBackground Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by mutations within the dystrophin gene. DMD is characterized by progressive skeletal muscle degeneration and atrophy and progressive cardiomyopathy. It has been observed the severity of cardiomyopathy varies in patients with DMD. Methods and Results A cohort of male patients with DMD and female DMD carriers underwent whole exome sequencing. Potential risk factor variants were identified according to their functional annotations and frequencies. Cardiac function of 15 male patients with DMD was assessed by cardiac magnetic resonance imaging, and various cardiac magnetic resonance imaging parameters and circulating biomarkers were compared between genotype groups. Five subjects carrying potential risk factor variants in the cystic fibrosis transmembrane regulator gene demonstrated lower left ventricular ejection fraction, larger left ventricular end‐diastolic volume, and higher NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels compared with 10 subjects who did not carry the potential risk factor variants (P=0.023, 0.019 and 0.028, respectively). Conclusions This study revealed heterozygous cystic fibrosis transmembrane regulator gene missense variants were associated with worse cardiac function in patients with DMD. The cystic fibrosis transmembrane regulator gene may serve as a genetic modifier that accounts for more severe cardiomyopathy in patients with DMD, who would require more aggressive management of the cardiomyopathy.https://www.ahajournals.org/doi/10.1161/JAHA.120.016799Duchene muscular dystrophy–associated cardiomyopathygenetic modifierwhole exome sequencing |
| spellingShingle | Xuan Jiang Yanqiu Shao Faris G. Araj Alpesh A. Amin Benjamin M. Greenberg Mark H. Drazner Chao Xing Pradeep P. A. Mammen Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease Duchene muscular dystrophy–associated cardiomyopathy genetic modifier whole exome sequencing |
| title | Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy |
| title_full | Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy |
| title_fullStr | Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy |
| title_full_unstemmed | Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy |
| title_short | Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy |
| title_sort | heterozygous cystic fibrosis transmembrane regulator gene missense variants are associated with worse cardiac function in patients with duchenne muscular dystrophy |
| topic | Duchene muscular dystrophy–associated cardiomyopathy genetic modifier whole exome sequencing |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.120.016799 |
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