中国儿童PAX2基因突变的临床表型和基因型分析  

Analysis of clinical phenotype and genotype of PAX2 mutation in Chinese children

作　　者：马雪晴 何永华 杨静[1] 徐荣荣 杨思莹 梁文沛 周建华[1] 袁惠卿[1] 仇丽茹[1] Ma Xueqing;He Yonghua;Yang Jing;Xu Rongrong;Yang Siying;Liang Wenpei;Zhou Jianhua;Yuan Huiqing;Qiu Liru(Nephrology Division of Department of Pediatrics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Pediatrics Department,Wuhan Central Hospital,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院儿童肾脏专科,武汉430030 [2]武汉市中心医院儿科,武汉430030

出　　处：《中华肾脏病杂志》2024年第1期24-35,共12页Chinese Journal of Nephrology

基　　金：湖北省科技计划重大专项(2020AEA009);湖北陈孝平科技发展基金会青年科学专项基金(CXPJJH11900018-2007);湖北省卫生健康委面上项目(WJ2023M004)。

摘　　要：目的总结和分析中国儿童PAX2基因突变的临床表型和基因型特征,为该疾病的监测、治疗和预后提供信息。方法该研究为病例系列分析研究。收集2014年1月至2022年12月华中科技大学同济医学院附属同济医院儿童肾脏专科PAX2基因突变患儿的临床资料,提取患儿外周血基因组DNA并进行全外显子组测序。检索PubMed、Medline、中国知网和万方数据库,归纳和总结中国PAX2基因突变患儿的临床、病理及基因型改变特征,并与该中心病例进行比较。结果该研究纳入13例PAX2基因突变患儿,男9例,女4例,其中尿检查异常12例,影像学检查双肾体积偏小7例,肾囊肿5例。临床表型为先天性肾脏和尿路畸形8例,肾-视神经乳头缺损综合征1例,血尿或蛋白尿3例。5例患儿接受了肾活检,表现为局灶节段性肾小球硬化C3肾小球病1例,局灶节段性肾小球硬化1例,薄基底膜病变1例,IgA肾病2例。13例患儿基因检测结果显示9例为新生突变,其中4种为新突变类型:c.321G>A、c.213-8C>G、c.63C>A、c.449C>T。76dupG(p.V26Gfs*28)突变型2例。文献检索到中国儿童PAX2基因突变病例51例,男32例,女19例。影像学检查示双肾体积偏小8例,肾囊肿13例。临床表型为先天性肾脏和尿路畸形28例,肾-视神经乳头缺损综合征17例,血尿或蛋白尿6例。7例接受过肾活检,局灶节段性肾小球硬化2例,微小病变1例,系膜增生性肾小球肾炎1例,IgA肾病1例,膜性肾病1例,局灶增生硬化性紫癜性肾炎伴肾小球肥大1例。34例为新生突变,12例突变来自父亲或母亲,其中5例父亲或母亲无临床表现,肾功能正常。76dupG(p.V26Gfs*28)突变型11例。结论中国儿童PAX2基因突变的临床表型和基因型具有多样性,PAX2基因突变最常见的临床表型为先天性肾脏和尿路畸形,c.76dupG(p.V26Gfs*28)为最常见的PAX2基因突变型。Objective To analyze and summarize the clinical,genotypic and pathological characteristics of children with PAX2 gene mutation in China,and to provide information for the monitoring,treatment and prognosis of the disease.Methods It was a case series analysis study.The clinical data of children with PAX2 gene mutation in Pediatric Nephrology Department,Tongji Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology from January 2014 to December 2022 were collected,and peripheral blood gene DNA was extracted and sequenced for whole exome sequencing.The clinical,pathological and genotypic characteristics of PAX2 gene variation of children in China were summarized by searching PubMed,Medline,China National Knowledge Infrastructure and Wanfang database and compared with the cases in this single center.Results Among the 13 children with PAX2 gene mutation,there were 9 males and 4 females,12 patients with abnormal urine tests,7 patients with small kidney volume by imaging examination,and 5 patients with renal cysts.The clinical phenotypes were congenital renal and urinary tract malformations in 8 cases,renal coloboma syndrome in 1 case,and hematuria or proteinuria in 3 cases.Five patients underwent renal biopsies,showing focal segmental glomerulosclerosis and C3 glomerulopathy in 1 case,focal segmental glomerulosclerosis in 1 case,thin basement membrane lesion in 1 case,and IgA nephropathy in 2 cases.The genetic testing in 13 children showed 9 de novo mutations and 4 new mutations of c.321G>A,c.213-8C>G,c.63C>A and c.449C>T.There were 2 cases of 76dupG(p.V26Gfs*28)mutant.A total of 51 Chinese children with PAX2 gene mutation were found in the literature search.There were 32 males and 19 females,8 cases with small kidney volume and 12 cases with renal cysts.The clinical phenotypes were congenital anomalies of kidney and urinary tract in 28 cases,renal coloboma syndrome in 17 cases,and hematuria or proteinuria in 6 cases.Seven patients underwent renal biopsies,including 2 cases with foca

关 键 词：儿童 突变 基因型 PAX2基因 肾-视神经乳头缺损综合征 遗传性肾脏病 

分 类 号：R725.9[医药卫生—儿科]