Familial hypertrophic cardiomyopathy associated with cardiac beta-myosin heavy chain and troponin I mutations.

摘要

We report an African American family with hypertrophic cardiomyopathy in which an individual with severe disease has alterations in two sarcomeric protein genes, cardiac beta-myosin heavy chain (MYH7) and troponin I (TNNI3). Each of her children has only one of these mutations. Although novel, the MYH7 mutation disrupts a conserved amino acid, and other missense substitutions at this position are known to cause disease. The TNNI3 alteration, replacing proline with serine (Pro82Ser), has been previously implicated in elderly-onset hypertrophic cardiomyopathy, although its pathogenicity is not clear. Proline in this position is conserved in all species, and its alteration to a serine is likely to result in a dramatic change in protein structure. We analyzed DNA from a panel of 100 healthy African Americans and found 3% carry the heterozygous TNNI3 missense allele that was identified in this family. Based on these findings, we propose that the TNNI3 Pro82Ser alteration is likely a disease-modifying mutation in a severely affected individual, and, furthermore, carriers of this alteration (3% of African Americans) might be at increased risk of late-onset cardiac hypertrophy.