Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients with hypertrophic cardiomyopathy.
OBJECTIVE
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 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 MYH7 mutations, HCM patients with MYH7 were 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 MYH7 mutations 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 MYH7 were 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.
Van Driest
Sara L
SL
Departments of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Jaeger
Michele A
MA
Ommen
Steve R
SR
Will
Melissa L
ML
Gersh
Bernard J
BJ
Tajik
A Jamil
AJ
Ackerman
Michael J
MJ
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D024723:Ventricular Myosins / Q000235:genetics*
D024723:Ventricular Myosins