title: Somatic MYH7, MYBPC3, TPM1, TNNT2 and TNNI3 mutations in sporadic hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous genetic heart disease characterized by left ventricular hypertrophy in the absence of another disease that could explain the wall thickening. Elucidation of the genetic basis of HCM lead to the identification of several genes encoding sarcomeric proteins, such as MYH7, MYBPC3, TPM1, TNNT2, and TNNI3. Sarcomeric genes are mutated in approximately 40% of HCM patients and a possible explanation for the incomplete yield of mutation-positive HCM may be somatic mutations.
  
  
  RESULTS
  We studied 104 unrelated patients with non-familial HCM. Patients underwent clinical evaluation and mutation screening of 5 genes implicated in HCM (MYH7, MYBPC3, TPM1, TNNT2, and TNNI3) in genomic DNA isolated from resected cardiac tissue; 41 of 104 were found to carry a mutation, but as several patients carried the same mutations, the total amount of different mutations was 37; 20 of these mutations have been previously described, and pathogenicity has been assessed. To determine the effect of the 17 new mutations an in silico assay was performed and it predicted that 4 variants were damaging mutations. All identified variants were also seen in the DNA isolated from the corresponding blood, which demonstrated the absence of somatic mutations.
  
  
  CONCLUSIONS
  Somatic mutations in MYH7, MYBPC3, TPM1, TNNT2, and TNNI3 do not represent an important etiologic pathway in HCM.
authors.affiliation: Instituto de Investigación Biomédica de la Universidad de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC)-Universidad de A Coruña.
authors.forename: Lucía
authors.initials: L
authors.lastname: Núñez
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: Gimeno-Blanes
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Rodríguez-García
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monserrat
authors.forename: Esther
authors.initials: E
authors.lastname: Zorio
authors.forename: Caroline
authors.initials: C
authors.lastname: Coats
authors.forename: Christopher G
authors.initials: CG
authors.lastname: McGregor
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: Hernandez del Rincón
authors.forename: Alfonso
authors.initials: A
authors.lastname: Castro-Beiras
authors.forename: Manuel
authors.initials: M
authors.lastname: Hermida-Prieto
mesh_terms: D000328:Adult; D000368:Aged; D024722:Cardiac Myosins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D014335:Tropomyosin / Q000235:genetics*; D020107:Troponin T / Q000235:genetics*; D000099163:Myosin Binding Protein C
chemical_list: D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D014335:Tropomyosin; D020107:Troponin T; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human; C545568:TNNT2 protein, human; C490775:TPM1 protein, human