Heterozygous Cystic Fibrosis Transmembrane Regulator Gene Missense Variants Are Associated With Worse Cardiac Function in Patients With Duchenne Muscular Dystrophy

Autor: Jiang, Xuan, Shao, Yanqiu, Araj, Faris G, Amin, Alpesh A, Greenberg, Benjamin M, Drazner, Mark H, Xing, Chao, Mammen, Pradeep PA
Rok vydání: 2020
Předmět:
Duchenne/ Becker Muscular Dystrophy
musculoskeletal diseases
Adult
Male
congenital
hereditary
and neonatal diseases and abnormalities
Cystic Fibrosis
Duchene muscular dystrophy–associated cardiomyopathy
Intellectual and Developmental Disabilities (IDD)
Left
Cystic Fibrosis Transmembrane Conductance Regulator
Cardiorespiratory Medicine and Haematology
Cardiovascular
Whole Exome Sequencing
Duchene muscular dystrophy-associated cardiomyopathy
Dystrophin
Rare Diseases
Clinical Research
Natriuretic Peptide
Genetics
Ventricular Dysfunction
2.1 Biological and endogenous factors
Humans
Genetic Predisposition to Disease
Muscular Dystrophy
Pediatric
genetic modifier
Human Genome
Brain
Stroke Volume
Duchenne
Magnetic Resonance Imaging
Peptide Fragments
Brain Disorders
Heart Disease
Orphan Drug
Cine
Musculoskeletal
Heart Function Tests
Mutation
Female
Missense
Cardiomyopathies
Zdroj: Journal of the American Heart Association, vol 9, iss 19
Popis: 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.
Databáze: OpenAIRE
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