[The genotype-phenotype correlation of MYH7 gene G15391A mutation and MYBPC3 gene G12101A mutation in familial hypertrophic cardiomyopathy].
OBJECTIVE
To reveal genotype-phenotype correlation of disease-causing gene mutations in Chinese hypertrophic cardiomyopathy (HCM) pedigree.


METHODS
Peripheral venous blood samples were collected from two Chinese HCM families and 120 healthy subjects were recruited as normal control. The full encoding exons and flanking sequences of the cardiac troponin T gene (TNNT2), beta-myosin heavy chain gene (MYH7) and myosin binding protein C gene (MYBPC3) were amplified with the polymerase chain reaction method, DNA sequencing was used to detect the mutation.


RESULTS
In ZZJ family, mutation G12101A was identified in exon 21 of MYBPC3 gene in 4 family members [the arginine (R) converted to histidine (H)]. In this pedigree, three out of eight family members were diagnosed as HCM and with a penetrance of 75%. In FHL family, mutation G15391A was identified in exon 23 of MYH7 gene in 3 family members [the glutamic acid (E) converted to lysine (K)]. In this pedigree, three out of six family members were diagnosed as HCM and with a penetrance of 100%. Echocardiography showed obstruction of left ventricular outflow tract in two out of the three HCM patients.


CONCLUSIONS
Our results showed that the G12101A mutation of MYBPC3 gene is the causal mutation of familial HCM with mild phenotype. The G15391A mutation of MYH7 gene is the causal mutation of familial HCM with malignant phenotype and a penetrance of 100%. Screening mutations in the MYH7 gene should be viewed as a reasonable procedure in obstructive HCM patients.
WANG
Hu
H
Sino-German Laboratory for Molecular Medicine, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
ZOU
Yu-bao
YB
WANG
Ji-zheng
JZ
SONG
Lei
L
SUN
Kai
K
SONG
Xiao-dong
XD
WANG
Xiao-jian
XJ
ZHANG
Chan-na
CN
HUI
Ru-tai
RT
D044466:Asian People / Q000235:genetics; D024722:Cardiac Myosins / Q000235:genetics*; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000208:ethnology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020107:Troponin T / Q000235:genetics; D000099163:Myosin Binding Protein C
D024722:Cardiac Myosins; D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D020107:Troponin T; D000099163:Myosin Binding Protein C; C501641:MYH7 protein, human