title: Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy.
abstract: Genotype-phenotype correlation of hypertrophic cardiomyopathy (HCM) has been challenging because of the genetic and clinical heterogeneity. To determine the mutation profile of Chinese patients with HCM and to correlate genotypes with phenotypes, we performed a systematic mutation screening of the eight most commonly mutated genes encoding sarcomere proteins in 200 unrelated Chinese adult patients using direct DNA sequencing. A total of 98 mutations were identified in 102 mutation carriers. The frequency of mutations in MYH7, MYBPC3, TNNT2 and TNNI3 was 26.0, 18.0, 4.0 and 3.5 % respectively. Among the 200 genotyped HCM patients, 83 harbored a single mutation, and 19 (9.5 %) harbored multiple mutations. The number of mutations was positively correlated with the maximum wall thickness. We found that neither particular gene nor specific mutation was correlated to clinical phenotype. In summary, the frequency of multiple mutations was greater in Chinese HCM patients than in the Caucasian population. Multiple mutations in sarcomere protein may be a risk factor for left ventricular wall thickness.
authors.affiliation: Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Beijing, 100037, People's Republic of China.
authors.forename: Yubao
authors.initials: Y
authors.lastname: Zou
authors.forename: Jizheng
authors.initials: J
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Yilu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Shuo
authors.initials: S
authors.lastname: Gao
authors.forename: Channa
authors.initials: C
authors.lastname: Zhang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xinxing
authors.initials: X
authors.lastname: Feng
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Yajie
authors.initials: Y
authors.lastname: Wu
authors.forename: Hongju
authors.initials: H
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Jia
authors.forename: Hu
authors.initials: H
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Chaowu
authors.initials: C
authors.lastname: Yan
authors.forename: Minjie
authors.initials: M
authors.lastname: Lu
authors.forename: Xianliang
authors.initials: X
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Song
authors.forename: Rutai
authors.initials: R
authors.lastname: Hui
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000150:complications* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000150:complications* / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype