title: [Clinical characteristics and WT1 genetic analysis of patients with steroid-resistant nephrotic syndrome accompanied with genitourinary malformations].
abstract: OBJECTIVE
  To analyze the clinical features and WT1 gene mutations in patients with steroid-resistant nephrotic syndrome (SRNS) accompanied with genitourinary malformations. The expression of podocyte molecules was also investigated in renal specimen of these WT1 mutated patients.
  
  
  METHODS
  From January 2005 to May 2007, 3 cases of SRNS accompanied with genitourinary malformations were involved in this study. The expression of podocyte molecules (nephrin, podocin, alpha-actinin 4, WT1 and CD2AP) in 2 cases was analyzed by immunofluorescence and immunohistochemistry; using PCR to amplify genomic DNA and RT-PCR to amplify WT1 cDNA. GeneScan and GeneScan software were used to quantify the ratio of +KTS/-KTS isoforms.
  
  
  RESULTS
  The age of onset of the 3 cases were 6 months, 1 year and 10 years, respectively. The age at diagnosis was 7 months, 9 years and 15 years, respectively. The phenotype of case 1 and case 3 was male accompanied with genitourinary malformations. Case 2 was phenotypic female. Karyotype analysis of the 3 cases revealed 46, XY. Each case was diagnosed as SRNS. Focal segmental glomerulosclerosis (FSGS) was confirmed in 2 cases. Podocyte molecular expression altered in renal tissues of 2 cases. WT1 staining was negative in case 1. WT1 expression in case 2 showed a diffuse nuclear staining with less obvious speckles compared with controls. WT1 IVS 9 + 5 G > A mutation was detected in case 2 and WT1 exon 9 1186 G > A mutation was detected in case 3. No WT1 mutation was detected in case 1.
  
  
  CONCLUSIONS
  Karyotype analysis and WT1 genetic analyzing should be performed for all female patients with early onset SRNS and in male patients with SRNS accompanied with genitourinary malformations. The abnormal ratio of +KTS/-KTS isoforms caused by WT1 mutations along with abnormal expression of podocyte molecules were involved in the pathogenesis of proteinuria.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Jian-guo
authors.initials: JG
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Hui-jie
authors.initials: HJ
authors.lastname: Xiao
authors.forename: Qing-feng
authors.initials: QF
authors.lastname: Fan
authors.forename: Na
authors.initials: N
authors.lastname: Guan
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Hong-wen
authors.initials: HW
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009404:Nephrotic Syndrome / Q000150:complications / Q000235:genetics*; D010641:Phenotype; D050199:Podocytes; D013256:Steroids; D014564:Urogenital Abnormalities / Q000150:complications / Q000235:genetics*; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D013256:Steroids; D025721:WT1 Proteins