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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 patient...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792368/ https://www.ncbi.nlm.nih.gov/pubmed/33003980 http://dx.doi.org/10.1161/JAHA.120.016799 |
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author | Jiang, Xuan Shao, Yanqiu Araj, Faris G. Amin, Alpesh A. Greenberg, Benjamin M. Drazner, Mark H. Xing, Chao Mammen, Pradeep P. A. |
author_facet | Jiang, Xuan Shao, Yanqiu Araj, Faris G. Amin, Alpesh A. Greenberg, Benjamin M. Drazner, Mark H. Xing, Chao Mammen, Pradeep P. A. |
author_sort | Jiang, Xuan |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7792368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77923682021-01-15 Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy Jiang, Xuan Shao, Yanqiu Araj, Faris G. Amin, Alpesh A. Greenberg, Benjamin M. Drazner, Mark H. Xing, Chao Mammen, Pradeep P. A. J Am Heart Assoc Brief Communication 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. John Wiley and Sons Inc. 2020-10-02 /pmc/articles/PMC7792368/ /pubmed/33003980 http://dx.doi.org/10.1161/JAHA.120.016799 Text en © 2020 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Brief Communication Jiang, Xuan Shao, Yanqiu Araj, Faris G. Amin, Alpesh A. Greenberg, Benjamin M. Drazner, Mark H. Xing, Chao Mammen, Pradeep P. A. Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy |
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 | Brief Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792368/ https://www.ncbi.nlm.nih.gov/pubmed/33003980 http://dx.doi.org/10.1161/JAHA.120.016799 |
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