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中华妇幼临床医学杂志(电子版) ›› 2013, Vol. 09 ›› Issue (03) : 323 -329. doi: 10.3877/cma.j.issn.1673-5250.2013.03.010

所属专题: 经典病例 文献

论著

36例儿童局灶节段性肾小球硬化的病因分析
李国民1, 徐虹1,*,*(), 高学武2, 翟亦晖1, 沈茜1, 张晓娥1, 安宇2, 方晓燕1   
  1. 1. 201102 上海,复旦大学附属儿科医院肾脏风湿科
    2. 复旦大学生物医学研究院和复旦大学附属儿科医院儿童发育与疾病医学转化中心
  • 收稿日期:2013-04-16 修回日期:2013-05-07 出版日期:2013-06-01
  • 通信作者: 徐虹

Causes Analysis of 36 Children With Focal Segmental Glomerulosclerosis

Guo­min LI1, Hong XU1(), Yi­hui ZHAI2, Xue­wu GAO1, qian SHEN1, Xiao­e ZHAO1, Yu AN2, Xiao­yan FANG1   

  1. 1. Children's Hospital of Fudan University, Shanghai 201102, China
  • Received:2013-04-16 Revised:2013-05-07 Published:2013-06-01
  • Corresponding author: Hong XU
  • About author:
    (Corresponding author: XU Hong, Email: )
引用本文:

李国民, 徐虹, 高学武, 翟亦晖, 沈茜, 张晓娥, 安宇, 方晓燕. 36例儿童局灶节段性肾小球硬化的病因分析[J]. 中华妇幼临床医学杂志(电子版), 2013, 09(03): 323-329.

Guo­min LI, Hong XU, Yi­hui ZHAI, Xue­wu GAO, qian SHEN, Xiao­e ZHAO, Yu AN, Xiao­yan FANG. Causes Analysis of 36 Children With Focal Segmental Glomerulosclerosis[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2013, 09(03): 323-329.

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MYO1E 8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 1979 to December 2011, 36 clinical 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, 9 and analysis of 42 mutation 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 10 FSGS children with clear causative lesion(27.8%), which were low birth weight infants(LBWI, 2 cases), minimal change disease(MCD, 2 cases), hepatitis C(1 case), vesicoureteral reflux(VUR, 1 case), Galloway-Mowat syndrome (GMS, 1 case), Denys-Drash syndrome (DDS, 1 case), IgA nephropathy (1 case)and familial FSGS (1 case). There were 26 FSGS children with unknown cause(72.2%). Gene and its mutation analysis were conducted in 6 follow-up FSGS children with unknown cause and 1 DDS children.2 children (including 1 DDS 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.

表1 8个基因共计42个相关突变位点
Table 1 42 position of mutations in 8 genes
表2 10例病因明确FSGS患儿的临床特点
Table 2 Clinical features of 10 FSGS patients with clear causative lesion
图1 2例WT1突变图(箭头示突变位点)
Figure 1 Sequencing of WT1 exon 8, 9(The arrows indicate mutant positions)
表3 6例坚持随访且病因不明FSGS患儿临床特点和基因突变位点结果
Table 3 Clinical features and position of mutations of 6 FSGS patients with unknown cause
表4 2例WT1突变患儿临床特点
Table 4 Clinical features of 2 WT1 mutations patients
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