摘要目的 探讨两个常染色体显性遗传多囊肾伴男性不育(adult polycystic kidney disease,ADPKD)家系的遗传学病因,为遗传咨询及产前诊断提供依据.方法 应用直接测序法对2个ADPKD家系进行PKD1和PKD2基因的突变检测,对可疑致病突变进行家系分析及生物信息学分析,并在50名正常对照者中进行突变筛查.结果 测序结果显示家系1先证者及另外3例患者的PKD1基因第16外显子存在c.6953_6977 del(p.Arg2318Hisfs* 15)杂合突变,2名表型正常的家系成员未检测到该位点突变.家系2先证者和另3例患者的PKD1基因第37外显子存在c.10937 T＞G(p.Va13646Gly)杂合突变,而2名表型正常的家系成员未检测到突变.经检索人类基因突变数据库(HGMD)这2个突变均为未报道过的新突变.通过家系分析及生物信息学分析结果显示这2个突变为致病突变的可能性大.在50名正常对照者未检测到该突变.结论 PKD1基因c.6953_6977 del(p.Arg2318Hisfs*15)和c.10937 T＞G(p.Val3646Gly)突变可能为这2个家系的致病原因,本研究结果丰富了PKD1基因突变谱及ADPKD表型谱,为家系遗传咨询和产前诊断提供了依据.

abstractsObjective To explore the genetic etiology of two Chinese pedigrees affected with autosomal dominant adult polycystic kidney disease and male infertility.Methods The coding regions of the PKD1 and PKD2 genes were subjected to PCR and Sanger sequencing.Suspected pathogenic mutations were analyzed by pedigree analysis and bioinformatics analysis.Mutation screening was performed using Sanger sequencing of blood samples obtained from 50 healthy individuals.Results Two novel heterozygous mutations,c.6953_6977 del(p.Arg2318Hisfs * 15) and c.10937 T＞G(p.Va13646Gly)of the PKD1 gene were identified in the affected members of the two pedigrees,respectively,but not among to normal family members of the two pedigrees.Pedigree and bioinformatics analysis showed that both mutations were pathogenic.No pathological mutations were found in the cohort of 50 healthy individuals.Conclusion Two novel mutations,c.6953_6977del(p.Arg2318Hisfs * 15) and c.10937 T＞ G(p.Val3646Gly) of the PKD1 gene may be responsible for the disease in the two pedigrees,which have enriched the spectrum of PKD1 gene mutations and provided a basis for genetic counseling and prenatal disgnosis.