Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy
SL Van Driest, VC Vasile, SR Ommen, ML Will… - Journal of the American …, 2004 - jacc.org
SL Van Driest, VC Vasile, SR Ommen, ML Will, AJ Tajik, BJ Gersh, MJ Ackerman
Journal of the American College of Cardiology, 2004•jacc.orgObjectives: We sought to determine the frequency and phenotype of mutations in myosin
binding protein C (MYBPC3) in a large outpatient cohort of patients with hypertrophic
cardiomyopathy (HCM) seen at our tertiary referral center. Background: Mutations in
MYBPC3 are one of the most frequent genetic causes of HCM and have been associated
with variable onset of disease and prognosis. However, the frequency of mutations and
associated clinical presentation have not been established in a large, unrelated cohort of …
binding protein C (MYBPC3) in a large outpatient cohort of patients with hypertrophic
cardiomyopathy (HCM) seen at our tertiary referral center. Background: Mutations in
MYBPC3 are one of the most frequent genetic causes of HCM and have been associated
with variable onset of disease and prognosis. However, the frequency of mutations and
associated clinical presentation have not been established in a large, unrelated cohort of …
Objectives
We sought to determine the frequency and phenotype of mutations in myosin binding protein C (MYBPC3) in a large outpatient cohort of patients with hypertrophic cardiomyopathy (HCM) seen at our tertiary referral center.
Background
Mutations in MYBPC3are one of the most frequent genetic causes of HCM and have been associated with variable onset of disease and prognosis. However, the frequency of mutations and associated clinical presentation have not been established in a large, unrelated cohort of patients.
Methods
Using deoxyribonucleic acid from 389 unrelated patients with HCM, each protein coding exon of MYBPC3was analyzed for mutations by polymerase chain reaction, denaturing high-performance liquid chromatography, and direct deoxyribonucleic acid sequencing. Clinical data were extracted from patient records blinded to patient genotype.
Results
Of 389 patients with HCM, 71 (18%) had mutations in MYBPC3. In all, 46 mutations were identified, 33 of which were novel (72%). Patients with MYBPC3mutations did not differ significantly from patients with thick filament-HCM, thin filament-HCM, or genotype-negative HCM with respect to age at diagnosis, degree of hypertrophy, incidence of myectomy, or family history of HCM or sudden death. Patients with multiple mutations (n = 10, 2.6%) had the most severe disease presentation.
Conclusions
This study defines the frequency and associated phenotype for MYBPC3and/or multiple mutations in HCM in the largest cohort to date. In this cohort, unrelated patients with MYBPC3-HCM virtually mimicked the phenotype of those with mutations in the beta-myosin heavy chain. Patients with multiple mutations had the most severe phenotype.
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