36例儿童局灶节段性肾小球硬化的病因分析

Causes Analysis of 36Children With Focal Segmental Glomerulosclerosis

目的探讨儿童局灶节段性肾小球硬化(FSGS)的病因。方法选择1979年1月至2011年12月于复旦大学附属儿科医院肾脏风湿科进行肾脏活检的36例FSGS患儿的临床资料为研究对象,对其临床特点进行回顾性分析,并经光学显微镜对其病理学结果进行分型。对坚持随访且病因不明的FSGS患儿进行常见FSGS致病基因NPHS2全部外显子组和WT1外显子8,9测序,并采用Snapshot技术对NPHS1,CD2AP,PLCε1,APOL1,TRPC6,INF2,MYH9和MYO1E8个相对少见致病基因的42个突变位点进行检测(本研究遵循的程序符合本院人体试验委员会所制定的伦理学标准,得到该委员会批准,并与患儿监护人签署临床研究知情同意书)。结果 36例FSGS患儿中,病因明确患儿为10例(27.8%),其中病因系低出生体重儿(LBWI)和微小病变肾病(MCD)患儿各为2例(5.6%),丙型肝炎、膀胱输尿管返流(VUR)、Galloway-Mowat综合征(GMS)、Denys-Drash综合征(DDS)、IgA肾病和家族性FSGS患儿各为1例(2.8%);病因不明患儿为26例(72.2%)。对坚持随访且病因不明的6例FSGS患儿和1例DDS患儿(共7例)进行相关基因和其突变位点分析发现,发生WTI突变患儿为2例(5.6%,包括1例DDS患儿),均为杂合性ARG394TRP突变。结论 FSGS病因较为复杂,LBWI是FSGS重要病因之一,应引起重视。病因不明患儿仍占FSGS患儿主体,部分病因不明FSGS患儿可能系相关致病基因突变引起,临床应利用遗传分子技术对该类患儿进行相关致病基因分析。

Objective To investigate the causes of children with focal segmental glomerulosclerosis（FSGS）.Methods From January 1979to December 2011,36clinical data of FSGS children who took renal biopsy were included in the study,and their clinical features were analyzed retrospectively.Sequencing of all NPHS2 exons,WT1 exon 8,9and analysis of 42mutation spots about NPHS1,CD2AP,PLCε1,APOL1,TRPC6,INF2,MYH9 and MYO1E by Snapshot technology were performed in follow-up patients with unknown cause FSGS.The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Children＇s Hospital of Fudan University.Results There were 10FSGS children with clear causative lesion（27.8%）,which were low birth weight infants（LBWI,2cases）,minimal change disease（MCD,2cases）,hepatitis C（1case）,vesicoureteral reflux（VUR,1case）,Galloway-Mowat syndrome（GMS,1case）,Denys-Drash syndrome（DDS,1case）,IgA nephropathy（1case）and familial FSGS（1case）.There were 26FSGS children with unknown cause（72.2%）.Gene and its mutation analysis were conducted in 6follow-up FSGS children with unknown cause and 1DDS children.2children（including 1DDS child）have WTI mutations which were both heterozygous ARG394TRP mutation.Conclusions Causes of FSGS are diverse,LBWI is one of the important causes of FSGS.FSGS children with unknown cause are still the majority,but pathogenic mutations may be found by gene analysis in these patients.We should use genetic molecular techniques to analyze unknown causes of FSGS in children.