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alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere

Item Type:Article
Title:alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere
Creators Name:Thierfelder, L.H. and Watkins, H. and MacRae, C. and Lamas, R. and McKenna, W. and Vosberg, H.P. and Seidman, J.G. and Seidman, C.E.
Abstract:We demonstrate that missense mutations (Asp175Asn; Glu180Gly) in the alpha-tropomyosin gene cause familial hypertrophic cardiomyopathy (FHC) linked to chromosome 15q2. These findings implicated components of the troponin complex as candidate genes at other FHC loci, particularly cardiac troponin T, which was mapped in this study to chromosome 1q. Missense mutations (Ile79Asn; Arg92Gln) and a mutation in the splice donor sequence of intron 15 of the cardiac troponin T gene are also shown to cause FHC. Because alpha-tropomyosin and cardiac troponin T as well as beta myosin heavy chain mutations cause the same phenotype, we conclude that FHC is a disease of the sarcomere. Further, because the splice site mutation is predicted to function as a null allele, we suggest that abnormal stoichiometry of sarcomeric proteins can cause cardiac hypertrophy.
Keywords:Amino Acid Sequence, Base Sequence, Hypertrophic Cardiomyopathy, Chromosome Mapping, DNA Primers, Complementary DNA, Linkage (Genetics), Molecular Sequence Data, Mutation, Phenotype, RNA Splicing, Sarcomeres, Tropomyosin, Troponin, Troponin T, Animals, Rats
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:77
Number:5
Page Range:701-712
Date:3 June 1994
Official Publication:https://doi.org/10.1016/0092-8674(94)90054-X
PubMed:View item in PubMed

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