title: [Beta-myosin heavy-chain gene mutations in patients with hypertrophic cardiomyopathy].
abstract: OBJECTIVE
  To determine the frequency of mutations in the beta-myosin heavy-chain gene (MYH7) in a cohort of patients with hypertrophic cardiomyopathy (HCM) and their families, and to investigate correlations between genotype and phenotype.
  
  
  METHODS
  Single-strand conformation polymorphism analysis and sequencing of fragments with abnormal MYH7 gene mobility were carried out in 128 consecutive index patients with HCM. The phenotypes of patients with and without mutations were compared and the phenotypes of identified families were recorded.
  
  
  RESULTS
  A total of 11 mutations were found in 13 families (10%); 7/11 had been previously described. The I736T mutation was found in three families and the A797T in two. One patient had two mutations (i.e., I736T and R787H). Mutations were more frequent in patients with a family history of sudden death (31%) and in those with severe hypertrophy (39% had a thickness > or = 30 mm). Mutations were found in 29 of 42 members of the 13 families, including six family members (20%) who were healthy carriers and aged < or = 36 years. Sudden death had occurred in eight members of four families: four in two families with the I736T mutation, one in a family with A797T, one in a family with R870H, and two in a family with A901P.
  
  
  CONCLUSIONS
  MYH7 mutations were present in 10% of our families. Mutations were more frequent in patients with a family history of sudden death and in those with severe hypertrophy. Most mutations had been described previously. Some appeared in several families. For some mutations, the correlation between genotype and phenotype was stable, while for others, there were marked differences between the phenotypes of the index patients and their relatives, suggesting the presence of additional genetic factors that have yet to be identified.
authors.affiliation: Servicio de Cardiología, Complejo Hospitalario Universitario Juan Canalejo e Instituto Universitario de Ciencias de la Salud de la Universidad de A Coruña, A Coruña, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Laredo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monserrat
authors.forename: Manuel
authors.initials: M
authors.lastname: Hermida-Prieto
authors.forename: Xusto
authors.initials: X
authors.lastname: Fernández
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodríguez
authors.forename: Laura
authors.initials: L
authors.lastname: Cazón
authors.forename: Inés
authors.initials: I
authors.lastname: Alvariño
authors.forename: Carlos
authors.initials: C
authors.lastname: Dumont
authors.forename: Pablo
authors.initials: P
authors.lastname: Piñón
authors.forename: Jesús
authors.initials: J
authors.lastname: Peteiro
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bouzas
authors.forename: Alfonso
authors.initials: A
authors.lastname: Castro-Beiras
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D024722:Cardiac Myosins / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000401:mortality; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003627:Data Interpretation, Statistical; D016757:Death, Sudden, Cardiac / Q000209:etiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains