A novel mutation of the beta myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy.
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder and shows high variability in genetic heterogeneity and phenotypic characteristics. The genetic etiology responsible for HCM in many individuals remains unclear.


OBJECTIVE
This instigation was sought to identify novel genetic determinants for familial hypertrophic cardiomyopathy.


METHODS
Six unrelated Chinese families with HCM were studied. For each of the 13 established HCM-susceptibility genes, 3 to 5 microsatellite markers were selected to perform genotyping and haplotype analysis. The linked genes were sequenced.


RESULTS
Haplotype analyses on candidate genetic loci revealed cosegregation of the gene beta-myosin heavy chain (MYH7) with HCM in a single family. A novel double heterozygous missense mutation of Ala26Val plus Arg719Trp in MYH7 was subsequently identified by sequencing in this family and was associated with a severe phenotype of HCM.


CONCLUSIONS
The novel double mutation of Ala26Val plus Arg719Trp in MYH7 identified in a Chinese family highlights the remarkable genetic heterogeneity of HCM, which provides important information for genetic counseling, accurate diagnosis, prognostic evaluation, and appropriate clinical management.
Wang
Juan
J
Department of Cardiovascular Medicine, East Hospital, Tongji University, Shanghai, China. Juan.Wang@mail.tongji.edu.cn
Xu
Shi-Jie
SJ
Zhou
Hua
H
Wang
Li-Jie
LJ
Hu
Bo
B
Fang
Fang
F
Zhang
Xu-Min
XM
Luo
Yi-Wei
YW
He
Xiao-Yan
XY
Zhuang
Shao-Wei
SW
Li
Xin-Ming
XM
Liu
Zhong-Ming
ZM
Hu
Da-Yi
DY
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D024722:Cardiac Myosins / Q000235:genetics*; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002681:China; D004252:DNA Mutational Analysis; D015150:Echocardiography, Doppler; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012307:Risk Factors; D012720:Severity of Illness Index
C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains