Niimura et al. (2002) reported an individual with late-onset hypertrophic cardiomyopathy (CMH7; 613690) in whom they found a missense mutation in the TNNI3 gene. The individual concerned had no family history of hypertrophic cardiomyopathy. The mutation, a C-to-T transition in exon 5, replaced proline with serine at amino acid position 82 (P82S). Proline-82 is highly conserved in mammalian, avian, and amphibian troponin I molecules.
In a 32-year-old African American woman with severe hypertrophic cardiomyopathy and a family history of CMH and sudden cardiac death, Frazier et al. (2008) identified a heterozygous P82S mutation in the TNNI3 gene and a heterozygous missense mutation in the MYH7 gene (160760.0043). Her affected 8-year-old daughter carried only the heterozygous MYH7 mutation, whereas her as yet unaffected 13-year-old son carried only the TNNI3 P82S variant. Frazier et al. (2008) suggested that the P82S variant, which they found in 3% of healthy African Americans, is a disease-modifying mutation in severely affected individuals, and that carriers of the variant might be at increased risk of late-onset cardiac hypertrophy.
