Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy

Sara L. Van Driest, Vlad C. Vasile, Steve R. Ommen, Melissa L. Will, A. Jamil Tajik, Bernard J. Gersh, Michael John Ackerman

Research output: Contribution to journalArticle

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Abstract

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. 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 patients. Using deoxyribonucleic acid from 389 unrelated patients with HCM, each protein coding exon of MYBPC3 was 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. 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 MYBPC3 mutations 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. This study defines the frequency and associated phenotype for MYBPC3 and/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.

Original languageEnglish (US)
Pages (from-to)1903-1910
Number of pages8
JournalJournal of the American College of Cardiology
Volume44
Issue number9
DOIs
StatePublished - Nov 2 2004

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Hypertrophic Cardiomyopathy
Mutation
Phenotype
Mutation Rate
myosin-binding protein C
Genotype
Ventricular Myosins
Myosin Heavy Chains
DNA
Sudden Death
Tertiary Care Centers
Hypertrophy
Exons
Outpatients
High Pressure Liquid Chromatography
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. / Van Driest, Sara L.; Vasile, Vlad C.; Ommen, Steve R.; Will, Melissa L.; Tajik, A. Jamil; Gersh, Bernard J.; Ackerman, Michael John.

In: Journal of the American College of Cardiology, Vol. 44, No. 9, 02.11.2004, p. 1903-1910.

Research output: Contribution to journalArticle

Van Driest, Sara L. ; Vasile, Vlad C. ; Ommen, Steve R. ; Will, Melissa L. ; Tajik, A. Jamil ; Gersh, Bernard J. ; Ackerman, Michael John. / Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. In: Journal of the American College of Cardiology. 2004 ; Vol. 44, No. 9. pp. 1903-1910.
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