一例由PAX2基因变异导致的Papillorenal综合征患者的遗传学分析  

Genetic analysis of a patient with Papillorenal syndrome due to variant of PAX2 gene

作　　者：赵学潮 郑玉婷 刘宁[1] 王聪慧 赵干业 张军军[2] 孔祥东[1] Zhao Xuechao;Zheng Yuting;Liu Ning;Wang Conghui;Zhao Ganye;Zhang Junjun;Kong Xiangdong(Genetics and Prenatal Diagnosis Center,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Institute of Nephrology,Department of Nephrology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院妇产医学部遗传与产前诊断中心,郑州450052 [2]郑州大学第一附属医院肾内科郑州大学肾脏研究所,郑州450052

出　　处：《中华医学遗传学杂志》2022年第10期1120-1123,共4页Chinese Journal of Medical Genetics

基　　金：河南省自然科学基金(202300410421)。

摘　　要：目的探讨1例临床表现为肾发育不全患者可能的分子遗传学病因。方法应用全外显子组测序对先证者进行基因变异分析,并通过Sanger测序对候选基因变异进行验证。应用PRS4-EGFP报告质粒分析位点变异对PAX2蛋白转录活性的影响。结果测序结果显示,先证者携带PAX2基因c.418C>T(p.Arg140Trp)杂合变异,为自发变异,已有文献报道与Papillorenal综合征相关。功能实验表明,PAX2-P130R、PAX2-R140G和PAX2-R140W对转录活性有显著抑制作用。而PAX2-A160T变异体对转录活性无影响。结论PAX2基因c.418C>T(p.Arg140Trp)杂合变异可能是先证者的遗传学病因,该变异可能导致孤立的肾发育不全。Objective To explore the genetic basis for a patient presenting with renal insufficiency.Methods The patient was subjected to whole exome sequencing,and the candidate variant was verified by Sanger sequencing.Transcriptional activity of the PAX2 gene was analyzed by using a PRS4-EGFP reporter plasmid.Results Genetic testing revealed that the patient has carried a novel de novo heterozygous variant c.418C>T(p.Arg140Trp)of the PAX2 gene.The influence of c.389C>G(p.Pro130Arg),c.478G>A(p.Ala160Thr),c.418C>G(p.Arg140Gly)and c.418C>T(p.Arg140Trp)variants on the transcriptional activity was also evaluated.Functional study has illustrated that the PAX2-P130R,PAX2-R140G and PAX2-R140W variants all had a significant inhibitory effect on the transcriptional activity,but not the PAX2-A160T variant.Conclusion The isolated renal hypoplasia of the proband is probably due to the likely pathogenic variant of the PAX2 gene.

关 键 词：Papillorenal综合征 PAX2基因 肾发育不全 转录活性 

分 类 号：R596[医药卫生—内科学]