Cardiomyopathy, Familial Hypertrophic, 7

A number sign (#) is used with this entry because familial hypertrophic cardiomyopathy-7 is caused by heterozygous mutation in the TNNI3 gene (191044) on chromosome 19q13.4.

For a general phenotypic description and a discussion of genetic heterogeneity of familial hypertrophic cardiomyopathy (CMH), see CMH1 (192600).

Clinical Features

Kimura et al. (1997) identified 6 probands with hypertrophic cardiomyopathy and mutations in the TNNI3 gene (CMH7). Three of these probands had ventricular hypertrophy characteristic of CMH; 3 others had apical hypertrophy (so-called Japanese-type CMH). The mutation-carrying son of one proband with apical hypertrophy had typical CMH. The 3 patients with apical hypertrophy carrying a G203S mutation (191044.0014) also exhibited Wolff-Parkinson-White ventricular preexcitation (WPW; 194200).

Niimura et al. (2002) presented data from a genetic analysis of 31 individuals with late-onset hypertrophic cardiomyopathy and no other family history. They identified 2 individuals with CMH7. The mean age of symptom development was 52.5 +/- 3.6 with a mean age at diagnosis of 49.0 +/- 9.9.

Arad et al. (2005) identified a proband with CMH7 with atrial fibrillation and apical cardiac hypertrophy. Five family members had undergone sudden cardiac death, and 3 additional mutation carriers in the family were found to have other CMH morphologies. In another family with the same mutation, the phenotype was primarily subaortic asymmetric hypertrophy.

Molecular Genetics

Kimura et al. (1997) analyzed the TNNI3 gene in 184 unrelated patients with CMH and identified 6 heterozygous mutations in 6 probands, respectively (see, e.g., 191044.0001 and 191044.0002). Although apical CMH had been associated particularly with CMH4 (115197), Kimura et al. (1997) found that 3 of 36 (8.3%) patients with apical CMH had mutations in the TNNI3 gene. In addition, all 3 individuals with the G203S mutation in the TNNI3 gene (191044.0014) exhibited Wolff-Parkinson-White ventricular preexcitation (WPW; 194200); Kimura et al. (1997) noted that although a locus for 'CMH with WPW' had been mapped to chromosome 7q3 (CMH6; 600858), their findings indicated that more than 1 form of CMH is associated with WPW syndrome.

Among 31 individuals with late-onset hypertrophic cardiomyopathy and no other family history, Niimura et al. (2002) identified 2 individuals with pathogenic mutations in the TNNI3 gene. Both reported mutations (191044.0003, 191044.0004) were missense mutations in conserved residues.

Arad et al. (2005) identified a heterozygous R21C mutation in the TNNI3 gene (191044.0016) in 2 families with CMH.