Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy
SL Van Driest, MA Jaeger, SR Ommen, ML Will… - Journal of the American …, 2004 - jacc.org
SL Van Driest, MA Jaeger, SR Ommen, ML Will, BJ Gersh, AJ Tajik, MJ Ackerman
Journal of the American College of Cardiology, 2004•jacc.orgObjectives: We sought to determine the prevalence and phenotype of beta-myosin heavy
chain gene MYH7 mutations in a large cohort of unrelated patients with hypertrophic
cardiomyopathy (HCM). Background: Hypertrophic cardiomyopathy is a heterogeneous
cardiac disease. MYH7 mutations are one of the most common genetic causes of HCM and
have been associated with severe hypertrophy, young age of diagnosis, and high risk of
sudden cardiac death. However, these clinical findings from large, family studies have not …
chain gene MYH7 mutations in a large cohort of unrelated patients with hypertrophic
cardiomyopathy (HCM). Background: Hypertrophic cardiomyopathy is a heterogeneous
cardiac disease. MYH7 mutations are one of the most common genetic causes of HCM and
have been associated with severe hypertrophy, young age of diagnosis, and high risk of
sudden cardiac death. However, these clinical findings from large, family studies have not …
Objectives
We sought to determine the prevalence and phenotype of beta-myosin heavy chain gene MYH7mutations in a large cohort of unrelated patients with hypertrophic cardiomyopathy (HCM).
Background
Hypertrophic cardiomyopathy is a heterogeneous cardiac disease. MYH7mutations are one of the most common genetic causes of HCM and have been associated with severe hypertrophy, young age of diagnosis, and high risk of sudden cardiac death. However, these clinical findings from large, family studies have not been confirmed in a large unrelated cohort.
Methods
Deoxyribonucleic (DNA) samples obtained from 389 HCM outpatients seen at this tertiary referral center were analyzed for mutations, using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing for all 38 protein-coding exons of MYH7. Clinical data were extracted from patient records blinded to patient genotype.
Results
Fifty-eight patients (15%) harbored 40 different mutations in MYH7. Compared with HCM patients without MYH7mutations, HCM patients with MYH7were younger at diagnosis (32.9 vs. 42.7 years, p = 0.0002), had more hypertrophy (left ventricular wall thickness of 24.2 vs. 21.1 mm, p = 0.0009), and more frequently underwent myectomy (60% vs. 38%, p = 0.002). The HCM patients with MYH7mutations more often had a family history of HCM (43% vs. 29%, p = 0.006), but there was no difference in family history of sudden death (16% vs. 14%, p = NS).
Conclusions
In this setting, HCM patients with MYH7were diagnosed at a younger age and had more hypertrophy, but they had no greater frequency of sudden death among first-degree relatives. Although these associations may prove useful for targeted gene screening, caution should be exercised in terms of using pathogenic status in risk stratification.
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