title: [Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy].
abstract: OBJECTIVE
  Mutation of a sarcomeric gene is the most frequent cause of hypertrophic cardiomyopathy. For each such gene, however, previous studies have reported a range of different mutation frequencies, and clinical manifestations have been highly heterogeneous, both of which limit the use of genetic information in clinical practice. Our aim was to determine the frequency of mutations in the sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in a cohort of Spanish patients with hypertrophic cardiomyopathy.
  
  
  METHODS
  We used sequencing to analyze the coding regions of these five genes in 120 patients (29% with a family history) and investigated how the patient phenotype varied with the gene mutated.
  
  
  RESULTS
  In total, 32 patients were found to have mutations: 10 in MYH7 (8%), 20 in MYBPC3 (16%), 2 in TNNT2, 1 in TPM1 and none in TNNI3. Overall, 61% of mutations had not been described before. Two patients had two mutations (i.e., double mutants). There was no difference in the mean age at diagnosis or the extent of the hypertrophy between those with MYH7 mutations and those with MYBPC3 mutations.
  
  
  CONCLUSIONS
  Some 26% of patients had a mutation in one of the five sarcomeric genes investigated. More than half of the mutations had not been described before. The MYBPC3 gene was the most frequently mutated, followed by MYH7. No phenotypic differences were observed between carriers of the various mutations, which makes it difficult to use genetic information to stratify risk in these patients.
authors.affiliation: Genética Molecular, Instituto de Investigación Nefrológica, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Castro
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Julián R
authors.initials: JR
authors.lastname: Reguero
authors.forename: José R
authors.initials: JR
authors.lastname: Berrazueta
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Belén
authors.initials: B
authors.lastname: Alonso
authors.forename: Rocío
authors.initials: R
authors.lastname: Sainz
authors.forename: María
authors.initials: M
authors.lastname: Martín
authors.forename: Cesar
authors.initials: C
authors.lastname: Morís
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012518:Sarcomeres / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D055815:Young Adult