46,XY Phenotypic Male With Focal Segmental Glomerulosclerosis Caused by the WT1 Splice Site Mutation

Horm Res. 2003;60(6):302-5. doi: 10.1159/000074249.


Objective: Frasier syndrome is characterized by progressive glomerulopathy due to nonspecific focal and segmental glomerulosclerosis (FSGS), 46,XY sex reversal and the development of gonadoblastoma from dysgenetic gonads. Donor splice site heterozygous mutations in intron 9 of the Wilms' tumor gene (WT1) cause this disease. We investigated whether WT1 mutations showed clinical heterogeneity.

Patients and methods: A 6-year-old phenotypic boy was diagnosed as having FSGS. His karyotype was 46,XY. Gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests revealed normal luteinizing hormone, follicle-stimulating hormone and testosterone responses. The other patient was a 7-year-old 46,XY female with FSGS. Prophylactic gonadectomy was performed and gonadoblastoma was found. By polymerase chain reaction and direct sequencing, WT1 was analyzed in these patients.

Results and conclusion: Both patients had IVS9 + 5G-->A in intron 9 of the WT1. Our study indicates a normal 46,XY phenotypic male patient with FSGS. The phenotypic variations of the WT1 splice site mutations are further expanded.

Publication types

  • Case Reports

MeSH terms

  • Child
  • Chorionic Gonadotropin
  • Denys-Drash Syndrome / complications
  • Denys-Drash Syndrome / genetics
  • Denys-Drash Syndrome / pathology
  • Female
  • Follicle Stimulating Hormone / blood
  • Gene Expression / genetics*
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease / genetics
  • Glomerulosclerosis, Focal Segmental / complications
  • Glomerulosclerosis, Focal Segmental / diagnosis*
  • Glomerulosclerosis, Focal Segmental / genetics
  • Gonadoblastoma / complications
  • Gonadoblastoma / diagnosis
  • Gonadoblastoma / genetics
  • Gonadotropin-Releasing Hormone
  • Humans
  • Introns / genetics
  • Japan
  • Luteinizing Hormone / blood
  • Male
  • Ovariectomy
  • Phenotype*
  • Point Mutation / genetics*
  • Polymerase Chain Reaction / methods
  • RNA Splice Sites / genetics*
  • Sequence Analysis, DNA / methods
  • Sex Chromosomes*
  • Testosterone / blood


  • Chorionic Gonadotropin
  • RNA Splice Sites
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone