title: Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome.
abstract: BACKGROUND
  Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant nephrotic syndrome (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes for end-stage renal disease (ESRD) in the first two decades of life. Sporadic mutations in the Wilms' tumor suppressor gene WT1 have been found to be present in patients with SRNS in association with Wilms' tumor (WT) and urinary or genital malformations, as well as in patients with isolated SRNS.
  
  
  METHODS
  To further evaluate the incidence of WT1 mutations in patients with NS we performed mutational analysis in 115 sporadic cases of SRNS and in 110 sporadic cases of steroid-sensitive nephrotic syndrome (SSNS) as a control group. Sixty out of 115 (52%) patients with sporadic SRNS were male, 55/115 (48%) were female. Sex genotype was verified by haplotype analysis. Mutational analysis was performed by direct sequencing and by denaturing high-performance liquid chromatography (DHPLC).
  
  
  RESULTS
  Mutations in WT1 were found in 3/60 (5%) male (sex genotype) cases and 5/55 (9%) female (sex genotype) cases of sporadic SRNS, and 0/110 (0%) sporadic cases of SSNS. One out of five female patients with mutations in WT1 developed a WT, 2/3 male patients presented with the association of urinary and genital malformations, 1/3 male patients presented with sexual reversal (female phenotype) and bilateral gonadoblastoma, and 4/5 female patients presented with isolated SRNS.
  
  
  CONCLUSIONS
  According to the data acquired in this study, patients presenting with a female phenotype and SRNS and male patients presenting with genital abnormalities should especially be screened to take advantage of the important genetic information on potential Wilms' tumor risk and differential therapy. This will also help to provide more data on the phenotype/genotype correlation in this patient population.
authors.affiliation: Departments of Pediatrics and Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Rainer G
authors.initials: RG
authors.lastname: Ruf
authors.forename: Michael
authors.initials: M
authors.lastname: Schultheiss
authors.forename: Anne
authors.initials: A
authors.lastname: Lichtenberger
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Karle
authors.forename: Isabella
authors.initials: I
authors.lastname: Zalewski
authors.forename: Bettina
authors.initials: B
authors.lastname: Mucha
authors.forename: Anne Schulze
authors.initials: AS
authors.lastname: Everding
authors.forename: Thomas
authors.initials: T
authors.lastname: Neuhaus
authors.forename: Ludwig
authors.initials: L
authors.lastname: Patzer
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.forename: Johannes P
authors.initials: JP
authors.lastname: Haas
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
authors.forename: Anita
authors.initials: A
authors.lastname: Imm
authors.forename: Arno
authors.initials: A
authors.lastname: Fuchshuber
authors.forename: Aysin
authors.initials: A
authors.lastname: Bakkaloglu
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004351:Drug Resistance; D005091:Exons; D005260:Female; D005838:Genotype; D018238:Gonadoblastoma / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D018309:Neoplasms, Gonadal Tissue / Q000453:epidemiology / Q000235:genetics; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics*; D010641:Phenotype; D015995:Prevalence; D013256:Steroids / Q000627:therapeutic use; D014564:Urogenital Abnormalities / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D013256:Steroids; D025721:WT1 Proteins