title: Lifelong left ventricular remodeling of hypertrophic cardiomyopathy caused by a founder frameshift deletion mutation in the cardiac Myosin-binding protein C gene among Japanese.
abstract: OBJECTIVE
  We studied the longitudinal evolution of hypertrophic cardiomyopathy (HCM) caused by a founder frameshift mutation in the cardiac myosin-binding protein C (MyBPC) gene.
  
  
  BACKGROUND
  Mutations in the MyBPC gene have been associated with delayed expression of HCM and a good prognosis. Few studies, however, demonstrated the phenotype-genotype correlations in the longitudinal study.
  
  
  METHODS
  We studied long-term evolution of clinical features of 15 unrelated families who were found to have an identical frameshift mutation in the MyBPC gene: a one-base deletion of a thymidine at nucleotide 11645 (V592fs/8).
  
  
  RESULTS
  Thirty-nine individuals in 15 families were genotype-positive. Thirty of the 39 individuals with the mutation were phenotype-positive. The disease penetrance was 100% in subjects > or =50 years and 65% in those <50 years. "End-stage" HCM (ejection fraction <50%) was observed in 7 (18%) of the 39 genotype-positive individuals (7 [23%] of the 30 phenotype-positive patients); 6 of them were 60 years or older. Seven patients were hospitalized for treatment of repeated congestive heart failure, and four patients died or had implantable cardioverter-defibrillator discharge (13%; incidence, 1.4%/year) during a mean follow-up period of 9.2 +/- 5.5 years.
  
  
  CONCLUSIONS
  Elderly patients with a V592fs/8 mutation in the MyBPC gene may evolve into the "end-stage" HCM, characterized by left ventricular systolic dysfunction, cavity dilation, and irreversible heart failure. The clinical course in patients with this mutation is not benign in the long run, with progressive left ventricular remodeling with advancing age.
authors.affiliation: Department of Medicine and Geriatrics, Kochi Medical School, Kochi, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kubo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kitaoka
authors.forename: Makoto
authors.initials: M
authors.lastname: Okawa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hitomi
authors.forename: Naohito
authors.initials: N
authors.lastname: Yamasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Furuno
authors.forename: Jun
authors.initials: J
authors.lastname: Takata
authors.forename: Masanori
authors.initials: M
authors.lastname: Nishinaga
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.forename: Yoshinori L
authors.initials: YL
authors.lastname: Doi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D017353:Gene Deletion; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D020257:Ventricular Remodeling / Q000235:genetics*; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C