title: Genotype/phenotype correlation in nephrotic syndrome caused by WT1 mutations.
abstract: OBJECTIVE
  The risk of developing Wilms tumor (WT) can be present or absent in patients with nephrotic syndrome (NS) caused by WT1 mutations. Here, the genotype/phenotype correlation regarding the outcome and risk for WT in 52 patients from 51 families with NS due to WT1 mutations is described.
  
  
  METHODS
  This study followed 19 patients with mutations in intron 9 splice donor site (KTS mutations), 27 patients with missense mutations, 4 patients with nonsense mutations, 1 patient with a splice site mutation in intron 8, and 1 patient with a deletion.
  
  
  RESULTS
  Twenty-four different WT1 mutations were detected. Sixteen of the 19 patients with KTS mutations were females. These patients had isolated NS if karyotype was 46,XX and Frasier syndrome if karyotype was 46,XY. Patients with KTS mutations presented at a significantly older age and with a slower progression toward chronic kidney disease (CKD) stage 5, compared with missense mutations. Patients with nonsense mutations presented initially with WT. Six patients with missense mutations developed WT after the diagnosis of NS (interval-range from NS onset to WT of 0.1 to 1.4 years).
  
  
  CONCLUSIONS
  (1) KTS mutations cause isolated NS with absence of WT in 46,XX females. (2) KTS mutations cause Frasier syndrome with gonadoblastoma risk in 46,XY phenotypic females. (3) KTS mutations cause NS with a slower progression when compared with missense mutations. (4) Missense mutations can occur with and without WT. (5) WT1 analysis is important in young patients with NS for early detection and tumor prophylaxis.
authors.affiliation: Departments of Pediatrics, University of Michigan Health System, Ann Arbor, MI 48109-5646, USA.
authors.forename: Gil
authors.initials: G
authors.lastname: Chernin
authors.forename: Virginia
authors.initials: V
authors.lastname: Vega-Warner
authors.forename: Dominik S
authors.initials: DS
authors.lastname: Schoeb
authors.forename: Saskia F
authors.initials: SF
authors.lastname: Heeringa
authors.forename: Bugsu
authors.initials: B
authors.lastname: Ovunc
authors.forename: Pawaree
authors.initials: P
authors.lastname: Saisawat
authors.forename: Roxana
authors.initials: R
authors.lastname: Cleper
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D052159:Frasier Syndrome / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D016162:Genes, Wilms Tumor; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018238:Gonadoblastoma / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007223:Infant; D007438:Introns; D007557:Israel; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D007680:Kidney Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009404:Nephrotic Syndrome / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D010375:Pedigree; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D017384:Sequence Deletion; D013997:Time Factors; D014421:Turkey; D014481:United States; D009396:Wilms Tumor / Q000208:ethnology / Q000235:genetics* / Q000401:mortality
chemical_list: D018389:Codon, Nonsense