title: Hypertrophic cardiomyopathy: low frequency of mutations in the beta-myosin heavy chain (MYH7) and cardiac troponin T (TNNT2) genes among Spanish patients.
abstract: BACKGROUND
  Mutations in the cardiac beta-myosin heavy chain (MYH7) and cardiac troponin T (TNNT2) genes are reportedly responsible for up to 40% of familial cases with hypertrophic cardiomyopathy (HC). Although there are no mutational hotspots, most of the mutations are located in specific exons of the MYH7 and TNNT2 genes. Currently it is not possible to predict the phenotype in carriers of mutations in these genes, although it is widely accepted that mutations in the MYH7 gene predispose to severe HC, whereas TNNT2 mutations are frequently linked to sudden cardiac death (SCD) in spite of minimal hypertrophy.
  
  
  METHODS
  We sequenced exons 8, 9, 13-16, 19, 20, 22-24, and 30 of the MYH7 gene and exons 8, 9, 11, and 14-16 of the TNNT2 gene in 30 HC patients (18-60 years of age) from the region of Asturias (Northern Spain); 25 cases (80%) had a family history of the disease. Genomic DNA was amplified, and fragments were directly sequenced. Each DNA variant found in the patients was also analyzed in 200 healthy controls through single-strand conformation analysis.
  
  
  RESULTS
  Four of the probands had nucleotide changes absent in the healthy controls. Two cases had mutations previously described in the MYH7 gene (exon 14, Arg453Cys) or the TNNT2 gene (exon 16, Arg278Cys). Two cases had new mutations (MYH7 exon 22, Met822Val; TNNT2 exon 14, Lys247Arg) not found among the healthy controls. We found MYH7 Met822Val in a woman with a severe form of HC; the mutation was absent in her parents, indicating a de novo mutation. MYH7 R453C was present in a woman with mild HC, mother of a son who died from SCD. TNNT2 R278C was present in a woman with severe HC, but a sister and a daughter were mutation carriers and did not have hypertrophy. A patient with severe HC was carrier of TNNT2 247Arg.
  
  
  CONCLUSIONS
  Mutations in the MYH7 and TNNT2 genes can be found in patients without a family history of HC. However, compared with other populations MYH7 or TNNT2 mutations were rare among our HC patients. This study illustrates the extreme phenotypic heterogeneity in carriers of MYH7 or TNNT2 mutations.
authors.affiliation: Genética Molecular-Instituto de Investigación Nefrológica (IRSIN-FRIAT) and. Servicio de Cardiología, Hospital Central de Asturias, 33006 Oviedo, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Castro
authors.forename: Julián R
authors.initials: JR
authors.lastname: Reguero
authors.forename: Alberto
authors.initials: A
authors.lastname: Batalla
authors.forename: Beatriz
authors.initials: B
authors.lastname: Díaz-Molina
authors.forename: Pelayo
authors.initials: P
authors.lastname: González
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Arturo
authors.initials: A
authors.lastname: Cortina
authors.forename: Gustavo I
authors.initials: GI
authors.lastname: Cubero
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D000293:Adolescent; D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D013030:Spain; D020107:Troponin T / Q000235:genetics*; D024723:Ventricular Myosins / Q000235:genetics*
chemical_list: D020107:Troponin T; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains