Lifelong left ventricular remodeling of hypertrophic cardiomyopathy caused by a founder frameshift deletion mutation in the cardiac Myosin-binding protein C gene among Japanese.
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.
Kubo
Toru
T
Department of Medicine and Geriatrics, Kochi Medical School, Kochi, Japan.
Kitaoka
Hiroaki
H
Okawa
Makoto
M
Matsumura
Yoshihisa
Y
Hitomi
Nobuhiko
N
Yamasaki
Naohito
N
Furuno
Takashi
T
Takata
Jun
J
Nishinaga
Masanori
M
Kimura
Akinori
A
Doi
Yoshinori L
YL
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
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C