title: Screening mutations in myosin binding protein C3 gene in a cohort of patients with Hypertrophic Cardiomyopathy.
abstract: BACKGROUND
  MyBPC3 mutations are amongst the most frequent causes of hypertrophic cardiomyopathy, however, its prevalence varies between populations. They have been associated with mild and late onset disease expression. Our objectives were to establish the prevalence of MyBPC3 mutations and determine their associated clinical characteristics in our patients.
  
  
  METHODS
  Screening by Single Strand Conformation Polymorphisms (SSCP) and sequencing of the fragments with abnormal motility of the MyBPC3 gene in 130 unrelated consecutive HCM index cases. Genotype-Phenotype correlation studies were done in positive families.
  
  
  RESULTS
  16 mutations were found in 20 index cases (15%): 5 novel [D75N, V471E, Q327fs, IVS6+5G>A (homozygous), and IVS11-9G>A] and 11 previously described [A216T, R495W, R502Q (2 families), E542Q (3 families), T957S, R1022P (2 families), E1179K, K504del, K600fs, P955fs and IVS29+5G>A]. Maximum wall thickness and age at time of diagnosis were similar to patients with MYH7 mutations [25(7) vs. 27(8), p = 0.16], [46(16) vs. 44(19), p = 0.9].
  
  
  CONCLUSIONS
  Mutations in MyBPC3 are present in 15% of our hypertrophic cardiomyopathy families. Severe hypertrophy and early expression are compatible with the presence of MyBPC3 mutations. The genetic diagnosis not only allows avoiding clinical follow up of non carriers but it opens new possibilities that includes: to take preventive clinical decisions in mutation carriers than have not developed the disease yet, the establishment of genotype-phenotype relationship, and to establish a genetic diagnosis routine in patients with familial HCM.
authors.affiliation: Hospital Universitario de A Coruña-Servicio Galego de Saúde (SERGAS), Instituto de Ciencias de la Salud, A Coruña, 15006, Spain.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Rodríguez-García
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monserrat
authors.forename: Martín
authors.initials: M
authors.lastname: Ortiz
authors.forename: Xusto
authors.initials: X
authors.lastname: Fernández
authors.forename: Laura
authors.initials: L
authors.lastname: Cazón
authors.forename: Lucía
authors.initials: L
authors.lastname: Núñez
authors.forename: Roberto
authors.initials: R
authors.lastname: Barriales-Villa
authors.forename: Emilia
authors.initials: E
authors.lastname: Maneiro
authors.forename: Elena
authors.initials: E
authors.lastname: Veira
authors.forename: Alfonso
authors.initials: A
authors.lastname: Castro-Beiras
authors.forename: Manuel
authors.initials: M
authors.lastname: Hermida-Prieto
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D019943:Amino Acid Substitution; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002353:Carrier State; D015331:Cohort Studies; D005190:Family; D005838:Genotype; D006720:Homozygote; D006801:Humans; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C