Fabry病在中国汉族肥厚型心肌病人群的患病率(英文)  

Prevalence of Fabry Disease in Chinese Patients with Hypertrophic Cardiomyopathy

作　　者：赵新涛[1] 陈伊[2] 冯新星[2] 宋莹[2] 王怡璐[2] 邹玉宝[2] 王继征[2] 惠汝太 邵一兵[1] 宋雷[2] 王旭[1] 

机构地区：[1]青岛大学医学院附属青岛市市立医院东院心内科,山东青岛266071 [2]中国医学科学院北京协和医学院阜外心血管病医院国家心血管病中心心血管转化医学国家重点实验室,北京100037

出　　处：《现代生物医学进展》2014年第11期2006-2010,共5页Progress in Modern Biomedicine

基　　金：the Ministry of Science and Technology of China(2010CB732601);the National Natural Science Foundation of China(30971233)~~

摘　　要：目的:研究中国汉族肥厚型心肌病人群中α-Galactosidase A突变的患病率及其临床表现。方法:对439名肥厚型心肌病患者及156名健康对照GLA基因进行全外显子测序,及基因型及临床表型进行关联分析。结果:确定了2个致病性突变,包括1个错义突变E66Q和1个剪接位点的突变c.547+1G>C。2个突变在156名健康人群未发现,在1000人基因组计划中未报道。确定中国汉族肥厚型心肌病人群中α-Galactosidase A突变0.45%的患病率。结论:Fabry病在中国汉族肥厚型心肌病人群中α-Galactosidase A突变的患病率较低。基因检测有助于Fabry病与肥厚型心肌病的鉴别诊断。Objective： To determine the prevalence and clinical manifestations of α-galactosidase A （GLA）mutations in chinese patients with hypertrophic cardiomyopathy （HCM）. Methods： GLA gene was sequenced in 439 patients with HCM and 156 healthy con-trols. Genotype and phenotype correlation was analyzed in patients with GLA mutations. Results： A total of 2 pathogenic mutations in GLA gene, including 1 splicing （c.547＋1G〉C） and 1 missense （E66Q）, was identified in 2 （0.45%） of 439 patients with HCM. All these mutations were lack in 156 healthy controls and not reported in either 1000 Genomes or Exome Sequencing Project. Bioinformatics anal-ysis showed these mutations had damaging effect on GLA protein or destroyed the existing splicing site. E66Q were known mutations, whereas c.547＋1G〉C were novel. No mutation in sarcomere genes was identified in the 2 patients with GLA mutations, indicating these mutations of GLA were independent causes of cardiac hypertrophy. One neutral rare variant （V256A） was also detected in 1 female pa-tient, who also carried a R671C mutation in MYH7. Various clinical manifestations were expressed in patients with GLA mutations, in-cluding, dyspnea in 1 patients, chest pain in 2 patients. The maximum left ventricle wall thickness was 15mm and 25mm. Resting ob-struction of left ventricular outflow tract were observed in 1 patiets. Thus, the clinical manifestations of patients with GLA mutation were not distinct from the typical HCM. Conclusions： The prevalence of fabry disease in Chinese patients with HCM was 0.45%. Genetic test-ing is helpful in differentiation of the two diseases.

关 键 词：肥厚型心肌病 FABRY病 患病率 突变 

分 类 号：R542.2[医药卫生—心血管疾病] R394.2[医药卫生—内科学]