Title. Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.
Authors. Hayashi T, Arimura T, Itoh-Satoh M, Ueda K, Hohda S, Inagaki N, Takahashi M, Hori H, Yasunami M, Nishi H, Koga Y, Nakamura H, Matsuzaki M, Choi BY, Bae SW, You CW, Han KH, Park JE, Knoll R, Hoshijima M, Chien KR, Kimura A.
Journal. J Am Coll Cardiol. 2004 Dec 7;44(11):2192-201.
Department of Molecular Pathogenesis, Medical Research Institute, and Laboratory of Genome Diversity, School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
Citation type: phenotype/genotype (clinical and genetic data).
Study design: candidate gene survey of patients with hypertrophic and dilated cardiomyopathy for TCAP mutations.
Study Summary: The Z-disk component Tcap, which associates into a titin/Tcap/MLP complex, was evaluated for sequence variation in 346 patients with hypertrophic cardiomyopathy and in 136 patients with dilated cardiomyopathy, of which 34 were familial and 102 were sporadic cases. One mutation was identified in a patient with DCM who had presented with heart failure at age 34 and underwent heart transplantation at age 35. The patient’s sister had died of SCD and heart failure at age 26, but DNA was not available for analysis. The patient’s father carried the TCAP mutation but did not have clinical disease. The patient’s mother and maternal uncle had hypertrophic cardiomyopathy, did not carry the TCAP mutation, but did carry a mutation in the gene for myosin protein binding C (MYBPC3). Two TCAP mutations were found in two families with hypertrophic cardiomyopathy. Additional
Comment: The modest clinical genetic data to support a disease-associated DCM phenotype was buttressed by two functional assays to suggest the identified mutation interferes with TCAP’s interaction with MLP, titin and calsarcin-1.