Clinical Research
Hypertrophic Cardiomyopathy
Comprehensive Analysis of the Beta-Myosin Heavy Chain Gene in 389 Unrelated Patients With Hypertrophic Cardiomyopathy

https://doi.org/10.1016/j.jacc.2004.04.039Get rights and content
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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.

DHPLC
denaturing high-performance liquid chromatography
HCM
hypertrophic cardiomyopathy
ICD
implantable cardioverter-defibrillator
LVWT
left ventricular wall thickness
MYH7
beta-myosin heavy chain gene
PCR
polymerase chain reaction
SCD
sudden cardiac death
SNP
single-nucleotide polymorphism

Cited by (0)

This study was supported by a Mayo Foundation Clinic Research (Mayo Foundation, Rochester, Minnesota) award to Dr. Ackerman, a Clinical Scientist Development Award from the Doris Duke Charitable Foundation, and the National Institutes of Health (HD42569), Bethesda, Maryland.