遗传性多囊肾家系PKD1、PKD2基因突变探讨与研究

Polycystic kidney family PKD1,PKD2 mutations to explore and research

目的对常染色体显性遗传多囊肾的PKD1、PKD2基因突变问题进行研究分析。方法采用二代外显子测序序列捕获技术,对常染色体显性遗传显性遗传性多囊肾系家族PKD1、PKD2基因进行测序,同时对8个家系的成员针对性的对基因突变的位点采取Sanger测序筛查,对通过Polyphen软件和SIF软件对基因突变的粗劣进行蛋白功能的测定。结果研究结果发现,PKD1基因存在一个框移突变C.2085-2086ins C为杂合子,这种氨基酸编码序列提前终止的现象既有可能影响蛋白质的功能;研究还发现存在两个错意突变杂合子,分别为p.Ala1447Val、p.Arg739Gln,其通过蛋白功能的检测初步预测其无害,同时还有两个同义变异,分别为p.Leu373Leu和p.Asn890Asn;而PKD2为基因为发现有框移突变、剪切、无义以及同义变异和措意变异等发生。同时发现在患病的家族成员中存在一个框移突变p.Ala696Argfs17X。正常的家族成员中未见此突变。结论研究初步发现,p.Ala696Argfs17X突变可能是导致常染色体显性遗传性多囊肾病的可疑治病突变。

Objective：Autosomal dominant polycystic kidney disease PKD1,PKD2 gene mutation analysis problems. Methods：The second generation of exon sequence capture technology,the autosomal dominant autosomal dominant polycystic kidney system family PKD1,PKD2 gene sequencing,while members of eight families targeted for mutations bit Point taken Sanger sequencing screening through Polyphen software and SIF software mutations crude protein function were measured. Results：The study found that,PKD1 gene there is a frame-shift mutation C.2085-2086 ins C heterozygous phenomenon this amino acid coding sequence early termination of both may affect the function of proteins;study also found that the presence of two heterozygous missense mutations,respectively p.Ala1447 Val,p.Arg739 Gln,its initial forecast by detecting its harmless protein function,as well as two synonymous mutation,respectively p.Leu373 Leu and p.Asn890 Asn;and PKD2 gene is found to have box frameshift mutations,cut,and synonymous mutation nonsense mutation and measures intended to occur. Also found that there is a frame-shift mutation p.Ala696 Argfs17 X in sick family members. Normal family members seen this mutation. Conclusion：Preliminary findings,p.Ala696 Argfs17 X mutations may lead to an autosomal dominant genetic mutation suspicious treatment of polycystic kidney disease.