[P1208fs mutation in the cardiac myosin binding protein C is associated with hypertrophic cardiomyopathy in a Chinese pedigree].
OBJECTIVE
To identify the potential mutations in a Chinese pedigree with hypertrophic cardiomyopathy (HCM), and to analyze the genotype-phenotype relationship in this pedigree.


METHODS
Clinical history and physical examinations, electrocardiography (ECG), echocardiography (UCG), cardiac magnetic resonance (CMR) data were obtained from 10 members of a three-generation Chinese family with HCM. A total of 96 genes related to hereditary cardiomyopathy were detected by exon and boarding intron analyses in the proband using second-generation sequencing. Mutations identified in the proband were confirmed by bi-directional Sanger sequencing in the rest 9 family members and 300 healthy controls.


RESULTS
Three mutations, including MYBPC3-P1208fs, ANK2-H556R and ANK2-P1974H, were identified in this pedigree. MYBPC3-P1208fs gene mutation was detected in 3 family members (proband, his mother and son), while this mutation was not detected in the rest family members. HCM was diagnosed in the proband and his mother by ECG, UCG and CMR. Son of the proband demonstrated early phenotype of HCM: although UCG and CMR were normal, ECG showed sinus bradycardia and paroxysmal supraventricular arrhythmias as well as ST segment changes. The onset age of HCM diagnosis of the proband and his mother was 42 and 50 years old, presented with palpitation and chest pain, and myocardial fibrosis sign in CMR. Furthermore, we found that left ventricular myocardial fibrosis is related to ECG changes (increasing r wave, ST segment change) in the proband and his mother. No HCM phenotype was evidenced in the 7 family members carrying ANK2-H556R and ANK2-P1974H mutations.


CONCLUSIONS
Our results show that MYBPC3-P1208fs gene mutation is associated HCM phenotype in this Chinses pedigree. This mutation is associated with myocardial fibrosis and ST changes in HCM phenotype in this pedigree while ANK2-H556R and ANK2-P1974H mutations are not related to HCM phenotype in this family.
Department of Graduate College of Ningxia Medical University, Yinchuan 750004, China.
J
J
Li
L W
LW
Liu
L S
LS
Na
L
L
Zuo
W
W
Qi
Y
Y
Liu
H
H
Shao
Z L
ZL
Ma
L F
LF
Wang
D044466:Asian People; D053840:Brugada Syndrome / Q000503:physiopathology; D000075224:Cardiac Conduction System Disease; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004452:Echocardiography; D004562:Electrocardiography; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009154:Mutation; D009206:Myocardium / Q000473:pathology; D010375:Pedigree; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D000099163:Myosin Binding Protein C