Skip to main content
NCBI home page
Heart logoLink to Heart
. 1996 Jul;76(1):63–65. doi: 10.1136/hrt.76.1.63

Clinical implications of hypertrophic cardiomyopathy associated with mutations in the alpha-tropomyosin gene.

K Yamauchi-Takihara 1, C Nakajima-Taniguchi 1, H Matsui 1, Y Fujio 1, K Kunisada 1, S Nagata 1, T Kishimoto 1
PMCID: PMC484428  PMID: 8774330

Abstract

OBJECTIVE: The disease-bearing genes for hypertrophic cardiomyopathy (HCM) in HCM families have been identified as the beta-myosin heavy chain, alpha-tropomyosin, and cardiac troponin T genes. Three HCM kindreds with three distinct point mutations in the alpha-tropomyosin gene had extensive clinical evaluations. DESIGN AND RESULTS: Single-strand conformation polymorphism gel analysis of polymerase chain reaction amplified products was used to capture each of the nine exons from the alpha-tropomyosin gene to identify mutations in 60 familial HCM patients. Two missense mutations in exon 2 (Ala63Val and Lys70Thr) and one missense mutation in exon 5 (Asp175Asn) were found in three unrelated HCM kindreds. These kindreds were the subject of clinical, electrocardiographic and echocardiographic studies. The morphological appearance of HCM was similar in the three kindreds. All the patients had severe hypertrophy of the left ventricle with asymmetrical septal hypertrophy during the early stage of the disease, which gradually progressed to dilatation of the left ventricle. Moreover, these kindreds showed similar disease penetrance, age of onset, and incidence of premature sudden death. The disease in these kindreds was severe and resulted in frequent sudden deaths. CONCLUSIONS: Among Japanese patients with familial HCM mutations in the alpha-tropomyosin gene are not as rare as reported, accounting for about 5% of all cases. These mutations are characterised by hypertrophy of the left ventricle which then progresses to dilatation and a high incidence of sudden or disease-related death.

Full text

PDF
63

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carrier L., Hengstenberg C., Beckmann J. S., Guicheney P., Dufour C., Bercovici J., Dausse E., Berebbi-Bertrand I., Wisnewsky C., Pulvenis D. Mapping of a novel gene for familial hypertrophic cardiomyopathy to chromosome 11. Nat Genet. 1993 Jul;4(3):311–313. doi: 10.1038/ng0793-311. [DOI] [PubMed] [Google Scholar]
  2. Hardy S., Fiszman M. Y., Osborne H. B., Thiebaud P. Characterization of muscle and non muscle Xenopus laevis tropomyosin mRNAs transcribed from the same gene. Developmental and tissue-specific expression. Eur J Biochem. 1991 Dec 5;202(2):431–440. doi: 10.1111/j.1432-1033.1991.tb16392.x. [DOI] [PubMed] [Google Scholar]
  3. Jarcho J. A., McKenna W., Pare J. A., Solomon S. D., Holcombe R. F., Dickie S., Levi T., Donis-Keller H., Seidman J. G., Seidman C. E. Mapping a gene for familial hypertrophic cardiomyopathy to chromosome 14q1. N Engl J Med. 1989 Nov 16;321(20):1372–1378. doi: 10.1056/NEJM198911163212005. [DOI] [PubMed] [Google Scholar]
  4. Maron B. J., Gottdiener J. S., Epstein S. E. Patterns and significance of distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy. A wide angle, two dimensional echocardiographic study of 125 patients. Am J Cardiol. 1981 Sep;48(3):418–428. doi: 10.1016/0002-9149(81)90068-0. [DOI] [PubMed] [Google Scholar]
  5. Nagata S., Park Y., Minamikawa T., Yutani C., Kamiya T., Nishimura T., Kozuka T., Sakakibara H., Nimura Y. Thallium perfusion and cardiac enzyme abnormalities in patients with familial hypertrophic cardiomyopathy. Am Heart J. 1985 Jun;109(6):1317–1322. doi: 10.1016/0002-8703(85)90358-8. [DOI] [PubMed] [Google Scholar]
  6. Nakajima-Taniguchi C., Matsui H., Eguchi N., Nagata S., Kishimoto T., Yamauchi-Takihara K. A novel deletion mutation in the beta-myosin heavy chain gene found in Japanese patients with hypertrophic cardiomyopathy. J Mol Cell Cardiol. 1995 Dec;27(12):2607–2612. doi: 10.1006/jmcc.1995.0047. [DOI] [PubMed] [Google Scholar]
  7. Nakajima-Taniguchi C., Matsui H., Nagata S., Kishimoto T., Yamauchi-Takihara K. Novel missense mutation in alpha-tropomyosin gene found in Japanese patients with hypertrophic cardiomyopathy. J Mol Cell Cardiol. 1995 Sep;27(9):2053–2058. doi: 10.1016/0022-2828(95)90026-8. [DOI] [PubMed] [Google Scholar]
  8. Ruiz-Opazo N., Nadal-Ginard B. Alpha-tropomyosin gene organization. Alternative splicing of duplicated isotype-specific exons accounts for the production of smooth and striated muscle isoforms. J Biol Chem. 1987 Apr 5;262(10):4755–4765. [PubMed] [Google Scholar]
  9. Takenaga K., Nakamura Y., Tokunaga K., Kageyama H., Sakiyama S. Isolation and characterization of a cDNA that encodes mouse fibroblast tropomyosin isoform 2. Mol Cell Biol. 1988 Dec;8(12):5561–5565. doi: 10.1128/mcb.8.12.5561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Thierfelder L., MacRae C., Watkins H., Tomfohrde J., Williams M., McKenna W., Bohm K., Noeske G., Schlepper M., Bowcock A. A familial hypertrophic cardiomyopathy locus maps to chromosome 15q2. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6270–6274. doi: 10.1073/pnas.90.13.6270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Thierfelder L., Watkins H., MacRae C., Lamas R., McKenna W., Vosberg H. P., Seidman J. G., Seidman C. E. Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere. Cell. 1994 Jun 3;77(5):701–712. doi: 10.1016/0092-8674(94)90054-x. [DOI] [PubMed] [Google Scholar]
  12. Watkins H., Anan R., Coviello D. A., Spirito P., Seidman J. G., Seidman C. E. A de novo mutation in alpha-tropomyosin that causes hypertrophic cardiomyopathy. Circulation. 1995 May 1;91(9):2302–2305. doi: 10.1161/01.cir.91.9.2302. [DOI] [PubMed] [Google Scholar]
  13. Watkins H., MacRae C., Thierfelder L., Chou Y. H., Frenneaux M., McKenna W., Seidman J. G., Seidman C. E. A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1q3. Nat Genet. 1993 Apr;3(4):333–337. doi: 10.1038/ng0493-333. [DOI] [PubMed] [Google Scholar]
  14. Watkins H., McKenna W. J., Thierfelder L., Suk H. J., Anan R., O'Donoghue A., Spirito P., Matsumori A., Moravec C. S., Seidman J. G. Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy. N Engl J Med. 1995 Apr 20;332(16):1058–1064. doi: 10.1056/NEJM199504203321603. [DOI] [PubMed] [Google Scholar]
  15. Yutani C., Imakita M., Ishibashi-Ueda H., Hatanaka K., Nagata S., Sakakibara H., Nimura Y. Three autopsy cases of progression to left ventricular dilatation in patients with hypertrophic cardiomyopathy. Am Heart J. 1985 Mar;109(3 Pt 1):545–553. doi: 10.1016/0002-8703(85)90561-7. [DOI] [PubMed] [Google Scholar]
  16. Zot A. S., Potter J. D. Structural aspects of troponin-tropomyosin regulation of skeletal muscle contraction. Annu Rev Biophys Biophys Chem. 1987;16:535–559. doi: 10.1146/annurev.bb.16.060187.002535. [DOI] [PubMed] [Google Scholar]

Articles from Heart are provided here courtesy of BMJ Publishing Group

RESOURCES