肺囊性纤维化一家系基因突变分析  

GENE MUTATION ANALYSIS OF ONE FAMILY OF PULMONARY CYSTIC FIBROSIS

作　　者：李梁珊 郭依侠 刘世国[1,2] 王丽娜[4] LI Liangshan;GUO Yixia;LIU Shi-guo;WANG Lina(Genetic Department,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院医学遗传科,山东青岛266003 [2]青岛大学附属医院产前诊断中心,山东青岛266003 [3]青岛大学附属医院儿童保健科,山东青岛266003 [4]青岛大学附属医院呼吸与危重症医学科,山东青岛266003

出　　处：《青岛大学学报（医学版）》2021年第4期503-506,共4页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金资助项目(30971586)。

摘　　要：目的对一个中国汉族肺囊性纤维化(PCF)的家系进行基因测序分析,寻找可疑致病基因突变,探讨疾病基因型和表型的关系。方法提取先证者外周静脉血全基因组DNA,利用全外显子测序(WES)进行突变筛查,与1000 genomes、dbSNP数据库中人类基因组参考序列进行比对,寻找可疑基因突变位点,采用一代测序在先证者及其父母中进行验证。结果先证者反复咳嗽2.5年,根据其临床表现、实验室检查结果和基因检测结果确诊为PCF。WES结果结合一代测序验证显示,病人的囊性纤维化跨膜传导调节因子(CFTR)基因存在两处复合杂合突变(c.650A>G/p.E217G、c.1231A>G/p.K411E,分别遗传自母亲和父亲),而在200例健康对照者中未发现该突变。结论CFTR基因c.650A>G、c.1231A>G复合杂合突变很可能是PCF的致病突变位点。本研究结果对扩大CFTR的突变谱和PCF的临床诊断及产前遗传学筛查具有重要意义。Objective To identify suspected pathogenic gene mutations by conducting the sequencing of a Chinese Han family of pulmonary cystic fibrosis(PCF),and to investigate the association between genotype and phenotype.Methods The whole genomic DNA was extracted from peripheral venous blood of the proband and whole exome sequencing(WES)was performed for mutation screening.The sequencing data were compared with the human reference sequence in 1000 genomes and dbSNP databases to identify suspected mutation loci,and Sanger sequencing was for verification in the proband and the parents.Results The proband had repeated cough for 2.5 years and was diagnosed with PCF according to clinical manifestations,laboratory examination results,and gene detection results.The results of WES and Sanger sequencing showed that there were two compound heterozygous mutations,c.650A>G/p.E217G and c.1231A>G/p.K411E,in the cystic fibrosis transmembrane conductance regulator(CFTR)gene,which were inherited from the mother and father,respectively,and these mutations were not detected in 200 healthy controls.Conclusion The compound heterozygous mutations,c.650A>G and c.1231A>G,in the CFTR gene may be the pathogenic mutations of PCF.The results of this study are of great significance for the supplement of the mutation spectrum of CFTR and the clinical diagnosis and prenatal genetic screening of PCF.

关 键 词：囊性纤维化 肺疾病 囊性纤维化跨膜传导调节因子 突变 全外显子组测序 

分 类 号：R563[医药卫生—呼吸系统] R394.3[医药卫生—内科学]