title: Familial hypertrophic cardiomyopathy associated with cardiac beta-myosin heavy chain and troponin I mutations.
abstract: 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.
authors.affiliation: Department of Pediatrics, Cardiology Division, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
authors.forename: Aisha
authors.initials: A
authors.lastname: Frazier
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.forename: Steven P
authors.initials: SP
authors.lastname: Schulman
authors.forename: Nicole
authors.initials: N
authors.lastname: Johnson
authors.forename: Kathryn W
authors.initials: KW
authors.lastname: Holmes
authors.forename: Anne M
authors.initials: AM
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D024722:Cardiac Myosins / Q000235:genetics*; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D019210:Troponin I / Q000235:genetics*
chemical_list: C501641:MYH7 protein, human; D019210:Troponin I; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains