【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.2085₂086ins 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。更多还原

【Abstract】 Objective: To analysis and identify mutations of PKD1,PKD2 gene in a Chinese family with Autosomal dominant polycystic 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 8family 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_ 2086 ins C( 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. Ala1447 Val,P. Arg739Gln) were harmless in PKD1 gene on prediction of protein function. Furthermore,the additional two synonymous mutations( p. Leu373 Leu,p. Asn890Asn) in PKD1 gene were identified. The coding region of PKD2 gene was not found frameshift,nonsense,shear,or synonymous mutations. The p. Ala696Argfs17 X 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.更多还原