| | |  | | | | Record from Web of Science® | | | | | | |
| ALPHA-TROPOMYOSIN AND CARDIAC TROPONIN-T MUTATIONS CAUSE FAMILIAL HYPERTROPHIC CARDIOMYOPATHY - A DISEASE OF THE SARCOMERE |
|
|
| Author(s): THIERFELDER L, WATKINS H, MACRAE C, LAMAS R, MCKENNA W, VOSBERG HP, SEIDMAN JG, SEIDMAN CE |
| Source: CELL Volume: 77 Issue: 5 Pages: 701-712 Published: JUN 3 1994 |
| Times Cited: 580 References: 47 |
| 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: THIERFELDER, L (reprint author), HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA |
Addresses:
1. HARVARD UNIV, SCH MED, HOWARD HUGHES MED INST, BOSTON, MA 02115 USA
2. BRIGHAM & WOMENS HOSP, DEPT MED, DIV CARDIOL, BOSTON, MA 02115 USA
3. MIL HOSP, NEONTOL UNIT, SANTIAGO, CHILE
4. ST GEORGE HOSP, SCH MED, DEPT CARDIOL SCI, LONDON SW17 0RE, ENGLAND
5. MAX PLANCK INST PHYSIOL & CLIN RES, D-61231 BAD NAUHEIM, GERMANY |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: NQ123 |
| ISSN: 0092-8674 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |