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. 2009 Feb 3;24(5):397–402. doi: 10.1002/clc.4960240510

Cardiac troponin T Arg92Trp mutation and progression from hypertrophic to dilated cardiomyopathy

Noboru Fujino 1, Masami Shimizu 1,✉, Hidekazu Ino 1, Kazuyasu Okeie 1, Masato Yamaguchi 1, Toshihiko Yasuda 1, Hiromasa Kokado 1, Hiroshi Mabuchi 1
PMCID: PMC6654954  PMID: 11346248

Abstract

Background: Mutations in the cardiac troponin T gene causing familial hypertrophic cardiomyopathy (HCM) are associated with a very poor prognosis but only mild hypertrophy. To date, the serial morphologic changes in patients with HCM linked to cardiac troponin T gene mutations have not been reported.

Hypothesis: The aim of this study was to determine the long‐term course of patients with familial HCM caused by the cardiac troponin T gene mutation, Arg92Trp.

Results: The Arg92Trp missense mutation was present in 10 individuals from two unrelated pedigrees. They exhibited different cardiac morphologies: three had dilated cardiomyopathy‐like features, five had asymmetric septal hypertrophy with normal left ventricular systolic function, one had electrocardiographic abnormalities without hypertrophy, and one had the disease‐causing mutation but did not fulfill the clinical criteria for the disease. The mean maximum wall thickness was 14.1 ± 6.0 mm. The three patients with dilated cardiomyopathy‐like features had progressive left ventricular dilation. Three individuals underwent right ventricular endomyocardial biopsy. There was a modest degree of myocardial hypertrophy (myocyte diameter: 18.9 ± 5.2 m̈m), and minimal myocardial disarray and mild fibrosis were noted.

Conclusion: The Arg92Trp substitution in the cardiac troponin T gene shows a high degree of penetrance, moderate hypertrophy, and early progression to dilated cardiomyopathy in Japanese patients. Early identification of individuals with this mutation may provide the opportunity to evaluate the efficacy of early therapeutic interventions.

Keywords: familial hypertrophic cardiomyopathy, cardiac troponin T gene mutation, dilated cardiomyopathy‐like features

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