[Family hypertrophic cardiomyopathy caused by a 14035c > t mutation in cardiac troponin T gene].
OBJECTIVE
To study the disease-causing gene mutation in Chinese patients with familial hypertrophic cardiomyopathy (FHC) and to analyze the correlation between the genotype and the phenotype.


METHODS
Peripheral blood samples were collected from 40 members from a family affected with FHC, and 120 healthy volunteers. PCR was performed to analyze the exons and flanking introns of the cardiac troponin T gene (TNNT2), beta-myosin heavy chain gene (MYH7), and myosin-binding protein C gene (MYBPC3) and the products were sequenced. The clinical data including symptom, physical examination, echocardiography and electrocardiography were collected.


RESULTS
A 14035c > t mutation, which causes a missense mutation (R130C) in exon 10 of TNNT2 gene were identified in 4 family members, including the proband, female, aged 53, with the onset at the age of 30. The 4 persons with the 14035c > t mutation, all FHC patients, presented left ventricular dysfunction with a penetrance of 100%. Two of the patients died of sudden cardiac death during follow-up. No mutation was identified in the MYH7 and MYBPC3 genes.


CONCLUSIONS
The 14035c > t mutation of TNNT2 gene is the causal mutation of FHC which is associated with malignant phenotype with a penetrance of 100%. It is a reasonable procedure in HCM patients with malignant phenotype to screen mutation in the TNNT2 gene.
Wang
Shu-Xia
SX
Sino-German Laboratory for Molecular Medicine, Fuwai Cardiovascular Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences, Beijing 100037, China.
Zou
Yu-Bao
YB
Fu
Chun-Yan
CY
Song
Lei
L
Wang
Hu
H
Wang
Ji-Zheng
JZ
Song
Xiao-Dong
XD
Chen
Jing-Zhou
JZ
Hui
Ru-Tai
RT
D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D020107:Troponin T / Q000235:genetics*
D020107:Troponin T