常染色体显性遗传性多囊肾家系PKD1、PKD2基因突变分析  

Detection of PKD1,PKD2 gene mutation in a Chinese family with autosomal dominant polycystic kidney disease

作　　者：骆杰伟[1,2] 孟晓嵘[1,2] 郑星宇[1,2] 魏世超[2] 胡丹[2] 杨笑[2] 张雪梅[2] 范丁前 

机构地区：[1]福建医科大学省立临床医学院,福州350001 [2]福建省立医院中医科

出　　处：《肾脏病与透析肾移植杂志》2014年第4期321-325,336,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：福建省自然科学基金项目(2013J01277);福建省中医药科研项目(wzsb201317)

摘　　要：目的:分析常染色体显性遗传性多囊肾病(ADPKD)家系基因突变位置及遗传特征。方法:应用二代测序外显子序列捕获技术,对ADPKD家系先证者PKD1、PKD2基因测序,并对8个家系成员针对突变位点进行Sanger测序筛查。并经SIF和Polyphen软件对基因突变进行蛋白功能预测。结果:发现PKD1基因1个框移突变c.2085_2086ins C(p.Ala696Argfs17X)为杂合子,造成PKD1氨基酸编码提前终止,很可能影响其蛋白功能;还发现2个错义突变杂合子(p.Ala1447Val和P.Arg739Gln,经蛋白功能预测为无害)及2个同义变异(p.Leu373Leu、p.Asn890Asn)。PKD2基因未发现框移、无义、剪切、错义或同义变异位点。其他患病的家系成员中发现p.Ala696Argfs17X突变,而正常成员中未查出此突变。结论:推测PKD1基因的框移突变(p.Ala696Argfs17X)为此家系的可疑致病性突变。Objective： To analysis and identify mutations of PKD1, PKD2 gene in a Chinese family with Autosomal dominant polyeystic kidney disease （ADPKD）. Methodology：To determine the genetic defects in proband with ADPKD by next-generation sequencing to capture exons of PKD1, PKD2 gene. Then, specific mutations of the 8 family members were detected by Sanger DNA sequencing, and the SIFT and Polyphen software were applied for protein function prediction about mutations. Results： The heterozygous frame shift mutation c. 2085 _ 2086insC （p.Ala696Argfs17X） in exon Tenth of PKD1 gene was detected, which mutation caused amino acid code code early termination. The finding two missense mutations （p.Ala1447Val, P：Arg739Gln） were harmless in PKD1 gene on prediction of protein function. Furthermore, the additional two synonymous mutations （p.Leu373Leu, p.Asn890Asn） in PKD1 gene were identified. The coding region of PKD2 gene was not found frameshift, nonsense, shear, or synonymous mutations. The p.Ala696ArgfslTX mutation was found in the other ADPKD family members, and was not found in normal members. Conclusion： We hypothesized that frame shift mutation （p.Ala696Argfs17X） in the PKD1 gene was suspicious pathogenic mutations in this family.

关 键 词：常染色体显性遗传性多囊肾 PKD1基因 PKD2基因 突变 

分 类 号：R692[医药卫生—泌尿科学]