Published online before print July 14, 2003, doi: 10.1161/01.CIR.0000080896.52003.DF
(Circulation. 2003;108:445.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Prevalence and Spectrum of Thin Filament Mutations in an Outpatient Referral Population With Hypertrophic Cardiomyopathy
From the Department of Molecular Pharmacology and Experimental Therapeutics (S.L.V.D., M.J.A.), Mayo Medical School (E.G.E.), Department of Internal Medicine/Division of Cardiovascular Diseases (S.R.O., A.J.T., B.J.G., M.J.A.), Department of Pediatric and Adolescent Medicine/Division of Pediatric Cardiology (A.J.T., M.J.A.), Mayo Clinic, Rochester, Minn.
Correspondence to Michael J. Ackerman, MD, PhD, Sudden Death Genomics Laboratory, Guggenheim 501, Mayo Clinic, Rochester, MN 55905. E-mail ackerman.michael{at}mayo.edu
Received February 26, 2003; revision received April 29, 2003; accepted May 5, 2003.
Background— Thin filament mutations are reported to cause 
20% of cases of hypertrophic cardiomyopathy (HCM), and they have been associated with specific phenotypes. However, the frequency of these mutations and their associated phenotype(s) from a large tertiary referral center population are unknown.
Methods and Results— DNA was obtained from 389 unrelated patients with HCM. A mutational analysis of all protein coding exons of cardiac troponin T, cardiac troponin I, 
-tropomyosin, and cardiac actin was performed using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing. The clinical data were extracted from patient records and maintained independent of the patient genotype. Overall, only 18 patients (4.6%) harbored isolated thin filament mutations: 8 had troponin T mutations, 6 had troponin I mutations, 3 had -tropomyosin mutations, and 1 had an actin mutation. Of the 12 unique missense mutations identified, 9 (75%) were novel mutations. As a group, patients with thin filament mutations were not significantly different from the rest of the cohort in age at diagnosis, left ventricular wall thickness, left ventricular outflow tract obstruction, or family history of HCM or sudden cardiac death.
Conclusions— Mutations in genes encoding thin filament proteins are less prevalent in HCM than previously estimated. Patients with mutations in troponin T, troponin I, -tropomyosin, and actin do not invariably present with any distinct clinical feature, thus limiting the utility of gene status for risk stratification or of clinical phenotype in guiding individual genetic screening at this time.
Key Words: hypertrophy • cardiomyopathy • genetics • death, sudden
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