常染色体显性多囊肾病家系的PDK1基因变异检测与产前诊断  

Analysis of PDK1 gene variants and prenatal diagnosis for eight pedigrees affected with autosomal dominant polycystic kidney disease

作　　者：李慧君 曹培暄 朱湘玉[1] 朱雨捷 吴星[1] 李洁[1] Li Huijun;Cao Peixuan;Zhu Xiangyu;Zhu Yujie;Wu Xing;Li Jie(Prenatal Diagnosis Center,the Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing,Jiangsu 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院妇产科,南京210008

出　　处：《中华医学遗传学杂志》2022年第9期932-937,共6页Chinese Journal of Medical Genetics

基　　金：2020年江苏省"双创计划"双创博士项目(苏人才办2020-2号)。

摘　　要：目的探讨8个多囊肾病家系的致病变异位点,为常染色体显性多囊肾病(autosomal dominant polycystic kidney disease,ADPKD)的遗传咨询和产前诊断提供理论依据。方法应用全外显子组测序和高通量测序技术检测8个独立家系中先证者的PKD1、PKD2基因,通过Sanger测序进行位点验证和家系分析,结合多囊肾疾病数据库和蛋白变异预测软件进行生物信息学分析。结果检测出8个PDK1变异,包括5个无义变异和3个错义变异。其中4个无义变异PDK1:c.7555C>T,c.7288C>T,c.4957C>T和c.11423G>A已报道为ADPKD的致病变异,1个错义变异PDK1:c.2180T>G(p.Leu727Arg)报道为可能致病的变异;3个变异位点未见报道,c.6781G>T(p.Glu2261*),c.109T>G(p.Cys37Gly),c.8495A>G(p.Asn2832Ser),其中无义变异PDK1 c.6781G>T(p.Glu2261*)为致病变异,错义变异PDK1 c.109T>G(p.Cys37Gly)和c.8495A>G(p.Asn2832Ser)为可能致病的变异。2个家系的产前诊断结果显示家系1胎儿携带与先证者相同的变异,家系2胎儿未携带与先证者相同的变异。结论鉴定出8个ADPKD家系的PDK1基因变异,其中包括3个未见报道的新变异,丰富了PDK1基因变异谱。以鉴定出的变异为理论依据,成功对2个家系进行产前诊断,为临床ADPKD出生缺陷提供咨询。Objective To detect potential variants in eight Chinese pedigrees affected with autosomal dominant polycystic kidney disease(ADPKD)and provide prenatal diagnosis for two of them.Methods Whole exome sequencing and high-throughput sequencing were carried out to detect variants of PKD1 and PKD2 genes in the probands.Sanger sequencing was used to validate the variants,and their pathogenicity was predicted by searching the ADPKD and protein variation databases.Results Eight PKD1 variants were detected,which have included five nonsense mutations and three missense mutations.Among these,four nonsense variants(PKD1:c.7555C>T,c.7288C>T,c.4957C>T,c.11423G>A)were known to be pathogenic,whilst one missense variant(PKD1:c.2180T>G)was classified as likely pathogenic.Three novel variants were detected,which included c.6781G>T(p.Glu2261*),c.109T>G(p.Cys37Gly)and c.8495A>G(p.Asn2832Ser).Prenatal testing showed that the fetus of one family has carried the same mutation as the proband,while the fetus of another family did not.Conclusion PKD1 variants,including three novel variants,have been identified in the eight pedigrees affected with ADPKD.Based on these results,prenatal diagnosis and genetic counseling have been provided.

关 键 词：常染色体显性多囊肾病 PDK1基因 基因变异 产前诊断 

分 类 号：R692[医药卫生—泌尿科学]