ClinVar

In a man who was diagnosed with hypertrophic cardiomyopathy (CMH23; see 612158) at 32 years of age, Theis et al. (2006) identified heterozygosity for a thr495-to-met (T495M) substitution in the ACTN2 gene. The patient had a maximum left ventricular wall thickness of 16 mm, with a sigmoid septal shape. He was treated with myectomy, and histopathologic analysis showed marked endocardial fibrosis, myocyte hypertrophy, and interstitial fibrosis. There was no family history of CMH or sudden cardiac death.

In a European and a South American proband with CMH, Chiu et al. (2010) identified heterozygosity for the T495M substitution in ACTN2, which the authors noted was located at a highly conserved residue within the second spectrin repeat of the rod domain. SNP analysis indicated that the mutation arose from different founders in the 2 families. One of the probands, who had an affected sister, also had a daughter who carried the T495M mutation. The 15-year-old girl had localized thickening of the interventricular septal wall, indicating early CMH. The other proband was a 20-year-old man with severe hypertrophy. His parents and sister were clinically unaffected but declined genetic testing. Chiu et al. (2010) noted that in contrast to the patient reported by Theis et al. (2006), none of these patients displayed sigmoidal morphology.