title: A frameshift deletion mutation in the cardiac myosin-binding protein C gene associated with dilated phase of hypertrophic cardiomyopathy and dilated cardiomyopathy.
abstract: OBJECTIVE
  A few studies reported that some mutations in the cardiac myosin-binding protein C (MyBPC) gene were associated with dilated phase of hypertrophic cardiomyopathy (D-HCM) resembling dilated cardiomyopathy (DCM). We studied 5 unrelated cardiomyopathy probands caused by an identical mutation in the MyBPC gene. The results of clinical and genetic investigations in these patients are presented in this paper.
  
  
  METHODS
  We analyzed MyBPC gene in DCM patients as well as patients with HCM.
  
  
  RESULTS
  An R945fs/105 mutation, 2-base deletion at nucleotides 18,535 and 18,536, was identified in 4 of the 176 HCM probands and in 1 of the 54 DCM probands. Genetic analysis in relatives of those probands revealed another one member with this mutation. A total of 6 subjects had R945fs/105 mutation. The mean age of these six patients at diagnosis was 61 years. At initial evaluation, three of them were diagnosed as having HCM with normal left ventricular (LV) systolic function. The other two patients already had D-HCM. The remaining one patient was diagnosed as having DCM because of reduced LV systolic function (ejection fraction=31%) without increased LV wall thickness. During follow-up (7.6 years), all three patients with impaired LV systolic function were admitted for treatment of heart failure and/or sustained ventricular tachycardia. Finally, one patient with the diagnosis of D-HCM died of heart failure.
  
  
  CONCLUSIONS
  The patients with this mutation may develop LV systolic dysfunction and suffer from cardiovascular events through mid-life and beyond.
authors.affiliation: Department of Medicine and Geriatrics, Kochi Medical School, Oko-cho, Nankoku-shi, Kochi 783-8505, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hitomi
authors.forename: Toru
authors.initials: T
authors.lastname: Kubo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kitaoka
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Hirota
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hamada
authors.forename: Eri
authors.initials: E
authors.lastname: Hoshikawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Hayato
authors.forename: Makoto
authors.initials: M
authors.lastname: Okawa
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.forename: Yoshinori L
authors.initials: YL
authors.lastname: Doi
mesh_terms: D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D054143:Heart Failure, Systolic / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C