title: A Novel Founder Mutation in MYBPC3: Phenotypic Comparison With the Most Prevalent MYBPC3 Mutation in Spain.
abstract: OBJECTIVE
  Mutations in MYBPC3 are the cause of hypertrophic cardiomyopathy (HCM). Although most lead to a truncating protein, the severity of the phenotype differs. We describe the clinical phenotype of a novel MYBPC3 mutation, p.Pro108Alafs*9, present in 13 families from southern Spain and compare it with the most prevalent MYBPC3 mutation in this region (c.2308+1 G>A).
  
  
  METHODS
  We studied 107 relatives of 13 index cases diagnosed as HCM carriers of the p.Pro108Alafs*9 mutation. Pedigree analysis, clinical evaluation, and genotyping were performed.
  
  
  RESULTS
  A total of 54 carriers of p.Pro108Alafs*9 were identified, of whom 39 had HCM. There were 5 cases of sudden death in the 13 families. Disease penetrance was greater as age increased and HCM patients were more frequently male and developed disease earlier than female patients. The phenotype was similar in p.Pro108Alafs*9 and in c.2308+1 G>A, but differences were found in several risk factors and in survival. There was a trend toward a higher left ventricular mass in p.Pro108Alafs*9 vs c.2308+1G>A. Cardiac magnetic resonance revealed a similar extent and pattern of fibrosis.
  
  
  CONCLUSIONS
  The p.Pro108Alafs*9 mutation is associated with HCM, high penetrance, and disease onset in middle age.
authors.affiliation: Unidad de Cardiopatías Hereditarias, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain. Electronic address: mariasm79es@hotmail.com.
authors.forename: María
authors.initials: M
authors.lastname: Sabater-Molina
authors.affiliation: Departamento de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Saura
authors.affiliation: Unidad de Cardiopatías Hereditarias, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Esperanza
authors.initials: E
authors.lastname: García-Molina Sáez
authors.affiliation: Departamento de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: González-Carrillo
authors.affiliation: Departamento de Patología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Polo
authors.affiliation: Unidad de Cardiopatías Hereditarias, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Pérez-Sánchez
authors.affiliation: Departamento de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: María Del Carmen
authors.initials: MDC
authors.lastname: Olmo
authors.affiliation: Departamento de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Oliva-Sandoval
authors.affiliation: Unidad de Cardiopatías Hereditarias, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Barriales-Villa
authors.affiliation: Centro de Bioquímica y Genética Clínica, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Carbonell
authors.affiliation: Departamento de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Domigo
authors.initials: D
authors.lastname: Pascual-Figal
authors.affiliation: Departamento de Cardiología, Hospital Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Gimeno
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004452:Echocardiography; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009218:Myosins; D010375:Pedigree; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate / Q000639:trends; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D004247:DNA; D009218:Myosins; D000099163:Myosin Binding Protein C
keywords: Cardiomyopathy; Hipertrofia; Hypertrophy; MYBPC3 mutation; Miocardiopatía; Muerte súbita; Mutación en MYBPC3; Proteína truncada; Sudden death; Truncated protein