Analysis of MYH7, MYBPC3 and TNNT2 gene mutations in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy and the correlation between genotype and phenotype.
- Author:
Wen-ling LIU
1
;
Wen-li XIE
;
Da-Yi HU
;
Tian-gang ZHU
;
Yun-tian LI
;
Yi-hong SUN
;
Cui-lan LI
;
Lei LI
;
Tian-chang LI
;
Hong BIAN
;
Qi-guang TONG
;
Song-na YANG
;
Rui-yun FAN
;
Wei CUI
Author Information
- Publication Type:Journal Article
- MeSH: Adolescent; Adult; Aged; Asian Continental Ancestry Group; genetics; Cardiac Myosins; genetics; Cardiomyopathy, Hypertrophic, Familial; ethnology; genetics; Carrier Proteins; genetics; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Mutation; Myosin Heavy Chains; genetics; Pedigree; Phenotype; Troponin T; genetics; Young Adult
- From: Chinese Journal of Cardiology 2006;34(3):202-207
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVEThe aim of this study was to screen the disease-causing gene mutations and investigate the genotype-phenotype correlation in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy (HCM).
METHODSThere are 91 family members from these 10 pedigrees and 5 members were normal mutated carriers, 23 members were HCM patients (14 male) aged from 1.5 to 73 years old. The functional regions of myosin heavy chain gene (MYH7), cardiac myosin-binding protein C (MYBPC3) and cardiac troponin T gene (TNNT2) were screened with PCR and direct sequencing technique. Clinical information from all patients was also evaluated in regard to the genotype.
RESULTSMutations were found in 5 out of 10 pedigrees. Mutations in MYH7 (Arg663His, Glu924Lys and Ile736Thr) were found in 3 pedigrees and 3 patients from these pedigrees suffered sudden death at age 20-48 years old during sport. Mutations in MYBPC3 were found in 2 pedigrees, 1 with complex mutation (Arg502Trp and splicing mutation IVS27 + 12C > T) and 1 with novel frame shift mutation (Gly347fs) and the latter pedigree has sudden death history. No mutation was identified in TNNT2.
CONCLUSIONSAlthough the Han Chinese is a relatively homogeneous ethnic group, different HCM gene mutations were responsible for familiar HCM suggesting the heterogeneity nature of the disease-causing genes and HCM MYH7 mutations are associated with a higher risk of sudden death in this cohort. Furthermore, identical mutation might result in different phenotypes suggesting that multiple factors might be involved in the pathogenesis of familiar HCM.