title: 46,XY phenotypic male with focal segmental glomerulosclerosis caused by the WT1 splice site mutation.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kusunoki
authors.forename: Testuro
authors.initials: T
authors.lastname: Nagashima
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nonomura
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
mesh_terms: D002648:Child; D006063:Chorionic Gonadotropin; D030321:Denys-Drash Syndrome / Q000150:complications / Q000235:genetics / Q000473:pathology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D015870:Gene Expression / Q000235:genetics*; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D018238:Gonadoblastoma / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010052:Ovariectomy; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D022821:RNA Splice Sites / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D012730:Sex Chromosomes; D013739:Testosterone / Q000097:blood
chemical_list: D006063:Chorionic Gonadotropin; D022821:RNA Splice Sites; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone