Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/0092-8674(94)90054-x

Type

Journal article

Journal

Cell

Publication Date

06/1994

Volume

77

Pages

701 - 712

Addresses

Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.

Keywords

Sarcomeres, Animals, Humans, Rats, Cardiomyopathy, Hypertrophic, Tropomyosin, Troponin, Troponin T, DNA, Complementary, DNA Primers, Chromosome Mapping, RNA Splicing, Amino Acid Sequence, Base Sequence, Phenotype, Mutation, Molecular Sequence Data, Genetic Linkage