Fabry病在中国汉族肥厚型心肌病人群的患病率(英文)

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+1GC。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。

Prevalence of Fabry Disease in Chinese Patients with Hypertrophic Cardiomyopathy

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.