常染色体显性多囊肾病的基因诊断与产前诊断  

Genetic diagnosis and prenatal diagnosis of autosomal dominant polycystic kidney disease

作　　者：邱碧原 杨季云 Qiu Biyuan;Yang Jiyun(Medical Technology College,Chengdu University of Traditional Chinese Medicine,Chengdu,Sichuan610075,China;Department of Laboratory Medicine,Zigong Women’s and Children’s Hospital,Zigong,Sichuan643000,China;Sichuan Provincial Key Laboratory for Human Disease Gene Study,Hospital of the University of Electronic Science and Technology,Sichuan Provincial People’S Hospital,Chengdu,Sichuan610072,China;School of Medicine,University of Electronic Science andTechnology,Chengdu,Sichuan610054,China;Prenatal Diagnosis Center,Hospital of the Universityof Electronic Science and Technology,Sichuan Provincial People’S Hospital,Chengdu,Sichuan610072,China)

机构地区：[1]成都中医药大学医学技术学院,610075 [2]自贡市妇幼保健院检验科,四川643000 [3]电子科技大学附属医院,四川省人民医院人类疾病基因研究重点实验室,成都610072 [4]电子科技大学医学院,成都610054 [5]电子科技大学附属医院,四川省人民医院产前诊断中心,成都610072

出　　处：《中华医学遗传学杂志》2019年第5期419-423,共5页Chinese Journal of Medical Genetics

基　　金：四川省科研院所科技成果转化资金项目(2016YSZH0032);成都市科技局科技惠民计划项目(2015-HM02-00094-SF).

摘　　要：目的 研究常染色体显性遗传多囊肾病(autosomal dominant polycystic kidney disease,ADPKD)的遗传病因,为家系的遗传咨询和产前诊断提供理论依据.方法 应用芯片捕获高通量测序检测17例先证者PKD1、PKD2基因,通过多个突变数据库过滤及生物信息学分析,并采用Sanger测序进行家系验证.对其中一个家系行产前基因诊断.结果 17例先证者中检出14个PKD1突变,3个PKD2突变,包括6个错义突变、4个无义突变、7个移码突变.其中,8个突变位点已报道与ADPKD相关,9个突变位点未报道过:PKD1:c.7625G>T(p.Gly2542Val),c.3673C>T(p.Gln1225*),c.11048dupT(p.Thr3684Aspfs* 38),c.9083_ 9084delAG (p.Glu3028Glyfs* 40),c.10560delG(p.Pro3521 Hisfs* 6),c.7952_7974 delTGTCCCTGAGGGTCCACACTGTG(p.Va12651Glyfs*2);PKD2:c.662T>G(p.Leu221*),c.1202_1203 insCT (p.Glu401Aspfs*2),c.919 delA (p.Ser307Valfs* 10).1个家系的产前基因检测结果显示胎儿未携带与先证者相同的突变.结论 明确了17个ADPKD家系的遗传病因,鉴定了PKD1、PKD2基因的9个未曾报道的新突变,丰富了ADPKD基因突变谱,为其遗传咨询和生育指导提供了理论依据.并成功对1个家系进行了产前诊断.Objective To explore the genetic etiology for 17 pedigrees affected with autosomal dominant polycystic kidney disease(ADPKD).Methods Peripheral blood samples were derived from the probands and their parents with informed consent.Following DNA extraction,targeted capture and next generation sequencing were carried out in search for potential disease-causing variants.Sanger sequencing was used to validate candidate pathogenic variants co-segregating with the disease in each pedigree.Prenatal diagnosis was provided for one family.Results Among the 17 probands,14 PKD1 mutations and 3 PKD2 mutations were detected,which included 6 missense mutations,4 nonsense mutations and 7 frameshift mutations.Of these,8 have been associated with ADPKD previously and 9 were novel,which included c.7625G>T(p.Gly2542Val),c.3673C>T(p.Gln1225*),c.11048dupT(p.Thr3684Aspfs*38),c.9083_9084delAG(p.Glu3028Glyfs*40),c.10560delG(p.Pro3521Hisfs*6),c.7952_7974del TGTCCCTGAGGGTCCACACTGTG(p.Val2651Glyfs*2)of PKD1,and c.662T>G(p.Leu221*),c.1202_1203 insCT(p.Glu401Aspfs*2),and c.919 delA(p.Ser307Valfs*10)ofPKD2.Prenatal testing showed that the fetus did not carry the same mutation as the proband.Conclusion Identification of causative mutations in the 17 pedigrees affected with ADPKD has provided a basis for genetic counseling and reproductive guidance.The novel mutations have enriched the spectrum of the PKD1 and PKD2 genes.

关 键 词：常染色体显性遗传多囊肾病 高通量测序 PKD1基因 PKD2基因 产前诊断 

分 类 号：R69[医药卫生—泌尿科学]