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

Aisha Frazier, Daniel P. Judge, Steven P. Schulman, Nicole Johnson, Kathryn W. Holmes, Anne M. Murphy

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


We report an African American family with hypertrophic cardiomyopathy in which an individual with severe disease has alterations in two sarcomeric protein genes, cardiac β-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.

Original languageEnglish (US)
Pages (from-to)846-850
Number of pages5
JournalPediatric Cardiology
Issue number4
StatePublished - Jul 2008
Externally publishedYes


  • Cardiomyopathy
  • Myosin heavy chain
  • Polymorphic modifier
  • Troponin I

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Cardiology and Cardiovascular Medicine


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