Other entities represented in this entry:
DO: 0110328;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 17q12 | Cardiomyopathy, hypertrophic, 25 | 607487 | Autosomal dominant | 3 | TCAP | 604488 |
A number sign (#) is used with this entry because of evidence that hypertrophic cardiomyopathy-25 (CMH25) is caused by heterozygous mutation in the TCAP gene (604488) on chromosome 17q12.
For a general phenotypic description and a discussion of genetic heterogeneity of hypertrophic cardiomyopathy, see CMH1 (192600).
Hayashi et al. (2004) studied 2 Japanese families with hypertrophic cardiomyopathy. In the first family, an affected mother and son both showed left ventricular hypertrophy (LVH) on electrocardiography (ECG), and the 62-year-old mother also exhibited Wolff-Parkinson-White syndrome (see 194200) whereas her 29-year-old son had abnormal Q-waves. The mother's father had died suddenly after exercise at 34 years of age. In the second family, a 67-year-old sister and 48-year-old brother had CMH; the sister showed LVH on ECG, whereas the brother had abnormal Q-waves. Two of their sibs had died suddenly after exercise, at 33 and 44 years of age.
Bos et al. (2006) reported a 65-year-old woman who was diagnosed with CMH at 44 years of age and who had massive hypertrophy, with a maximum left ventricular wall thickness of 46 mm. Although she was asymptomatic at presentation, she later developed dyspnea. She was treated with myectomy and a pacemaker. Family history included CMH but not sudden cardiac death. Reporting on the same patient, Theis et al. (2006) noted that she exhibited a sigmoid septal shape and that histopathologic examination of cardiac tissue from the myectomy procedure showed severe myocyte hypertrophy with moderate interstitial fibrosis.
The transmission pattern of CMH25 in the families reported by Hayashi et al. (2004) was consistent with autosomal dominant inheritance.
Following a screen of 10 known CMH-associated genes in 346 patients with CMH, Hayashi et al. (2004) directly sequenced the TCAP gene and identified heterozygosity for 2 different TCAP missense mutations, T137I (604488.0004) and R153H (604488.0005), in 2 Japanese probands who were negative for mutation in the known genes. The mutations, which segregated with disease in each family, were not found in 240 Japanese and 70 Korean controls.
In a cohort of 389 unrelated patients with CMH, Bos et al. (2006) screened for mutations in the 8 CMH-associated myofilament genes and in the 3 Z-disc genes TTN (188840), CSRP3 (600824), and TCAP. A variant was detected in the TCAP gene in 4 of the patients (see, e.g., R70W, 604488.0006).
Reclassified Variants
The R87Q variant (604488.0003) reported by Knoll et al. (2002) in a patient with dilated cardiomyopathy, previously designated in OMIM as CMD1N, has been reclassified as a variant of unknown significance. In a patient with dilated cardiomyopathy, Knoll et al. (2002) identified a heterozygous mutation in the TCAP gene (R87Q; 604488.0003).
Bos, J. M., Poley, R. N., Ny, M., Tester, D. J., Xu, X., Vatta, M., Towbin, J. A., Gersh, B. J., Ommen, S. R., Ackerman, M. J. Genotype-phenotype relationships involving hypertrophic cardiomyopathy-associated mutations in titin, muscle LIM protein, and telethonin. Molec. Genet. Metab. 88: 78-85, 2006. [PubMed: 16352453] [Full Text: https://doi.org/10.1016/j.ymgme.2005.10.008]
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., and 10 others. Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. J. Am. Coll. Cardiol. 44: 2192-2201, 2004. [PubMed: 15582318] [Full Text: https://doi.org/10.1016/j.jacc.2004.08.058]
Knoll, R., Hoshijima, M., Hoffman, H. M., Person, V., Lorenzen-Schmidt, I., Bang, M.-L., Hayashi, T., Shiga, N., Yasukawa, H., Schaper, W., McKenna, W., Yokoyama, M., and 9 others. The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 111: 943-955, 2002. [PubMed: 12507422] [Full Text: https://doi.org/10.1016/s0092-8674(02)01226-6]
Theis, J. L., Bos, J. M., Bartleson, V. B., Will, M. L., Binder, J., Vatta, M., Towbin, J. A., Gersh, B. J., Ommen, S. R., Ackerman, M. J. Echocardiographic-determined septal morphology in Z-disc hypertrophic cardiomyopathy. Biochem. Biophys. Res. Commun. 351: 896-902, 2006. [PubMed: 17097056] [Full Text: https://doi.org/10.1016/j.bbrc.2006.10.119]