一个常染色体显性遗传性多囊肾病家系的PKD1基因新剪切位点突变  

Identification of a novel splicing mutation of PKD1 gene in a pedigree affected with autosomal dominant polycystic kidney disease

作　　者：徐佩文[1] 邹洋[1] 李杰[1] 黄色新[1] 高明[1] 康冉冉 高媛[1] 

机构地区：[1]山东大学生殖医学研究中心、国家辅助生殖与优生工程技术研究中心、生殖内分泌教育部重点实验室,济南250001

出　　处：《中华医学遗传学杂志》2016年第6期778-781,共4页Chinese Journal of Medical Genetics

摘　　要：目的确定一个常染色体显性遗传多囊。肾病家系的PKD1基因突变。方法用测序方法检测先证者PKD1基因，并验证家系中其他成员及40名正常对照，再用反转录一PcR技术检测相应的mRNA序列的变化。结果基因测序结果显示该家系中5例患者均发生PKD1基因c．8791＋1_8791＋5delGTGCG（IVS23＋1_＋5delGTGCG）突变，mRNA序列分析证实该突变造成该基因mRNA的第23外显子3’端插入8个碱基序列。在表型正常亲属及正常对照中均未检测到该突变。结论本研究发现的PKD1基因c．8791＋1_8791＋5delGTGCG突变可影响mRNA的剪切，导致移码突变，可能是该常染色体显性遗传多囊肾病家系的致病原因。本研究结果进一步丰富了PKD1基因的突变谱。Objective To identify potential mutations of PKD1 gene in a family affected with autosomal dominant polycystic kidney disease （ADPKD）. Methods The coding regions of the PI（DI gene were subjected to PCR and Sanger sequencing. Reverse transcription-PCR （RT-PCR） was used to determine the relative mRNA expression in the patient. Results A splicing site mutation, c. 8791 ＋ 1_8791 ＋ 5delGTGCG （IVS23＋1_ ＋5delGTGCG）, was detected in the PKD1 gene in all 5 patients from the pedigree but not in 6 phenotypically normal relatives and 40 healthy controls. Sequencing of RNA has confirmed that there were 8 bases inserted in the 3r end of exon 23 of the PKD1 gene. Conclusion The novel c. 8791＋1_ 8791 ＋5delGTGCG mutation has created a new splice site and led to a frameshift, which probably underlies the ADPKD in the family. Above finding has enriched the mutation spectrum of the PKD1 gene.

关 键 词：常染色体显性遗传多囊肾病 PKD1基因 剪切突变 

分 类 号：R692[医药卫生—泌尿科学]