内蒙古地区家族性高胆固醇血症致冠心病患者基因筛查

Gene Screening for Familial Hypercholesterolemia-Related Coronary Heart Disease in Patients from Inner Mongolia

摘要: 目的：筛查内蒙古地区FH患者基因突变，了解FH基因突变与冠心病关系，为FH的发病机制提供重要的遗传学依据。方法：收集内蒙古地区20例家族性高胆固醇血症患者外周血，进行外显子测序。将得到的参考序列进行生物信息分析，经数据过滤及已知致病基因筛选后，获得12位患者相关致病突变。运用Sanger测序进行验证，排除可能的多态性，最后运用生物信息学软件对突变位点进行功能预测，确定致病突变。结果：经过全外显子测序、公共数据库过滤、突变筛选以及生物信息学分析后筛查10个LDLR基因突变，突变位点分别是：c.1448G>A、c.1860G>A、c.605T>C、c.2416InsG、c.1216C>A、g.17327G>A、c.2000delG、c.763T>C、c.1253A>G、g.13426G>A。结论：本研究在12名患者中筛查出内蒙古地区FH基因的致病突变，我们的发现为内蒙古地区FH的遗传咨询提供了理论支持与基础。

Abstract: Objective: To screen for gene mutations in patients with familial hypercholesterolemia (FH) in Inner Mongolia region, to understand the relationship between FH gene mutations and coronary heart disease, and to provide important genetic evidence for the pathogenesis of FH. Methods: Peripheral blood samples were collected from 20 patients with familial hypercholesterolemia in Inner Mongolia region, and exome sequencing was performed. The obtained reference sequences were analyzed by bioinformatics. After data filtering and screening of known pathogenic genes, the relevant pathogenic mutations of 12 patients were obtained. Sanger sequencing was used for verification to exclude possible polymorphisms. Finally, bioinformatics software was used to predict the functions of the mutation sites to determine the pathogenic mutations. Results: After whole exome sequencing, filtering through public databases, mutation screening, and bioinformatics analysis, 10 LDLR gene mutations were screened out. The mutation sites were: c.1448G>A, c.1860G>A, c.605T>C, c.2416InsG, c.1216C>A, g.17327G>A, c.2000delG, c.763T>C, c.1253A>G, g.13426G>A. Conclusion: In this study, the pathogenic mutations of FH genes in Inner Mongolia region were screened out in 12 patients. Our findings provide a theoretical support and basis for genetic counseling of FH in Inner Mongolia region.