title: Focal segmental glomerulosclerosis in patients with complete deletion of one WT1 allele.
abstract: The renal prognosis of patients with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation syndrome (WAGR) is poor. However, the renal histology and its mechanisms are not well understood. We performed renal biopsies in 3 patients with WAGR syndrome who had heavy proteinuria. The complete deletion of one WT1 allele was detected in each patient by constitutional chromosomal deletion at 11p13 using G-banding, high-resolution G-banding, and fluorescence in situ hybridization. The patients exhibited proteinuria at the ages of 6, 10, and 6 years and were diagnosed as having focal segmental glomerulosclerosis (FSGS) at the ages of 7, 16 and 19 years, respectively. They exhibited normal or mildly declined renal function at the time of biopsy. Re-examination of a nephrectomized kidney from 1 patient revealed that some glomeruli showed segmental sclerosis, although he did not have proteinuria at the time of nephrectomy. The other 2 patients did not develop Wilms' tumor and thus did not undergo nephrectomy, chemotherapy, or radiotherapy, thereby eliminating any effect of these therapies on the renal histology. In conclusion, complete deletion of one WT1 allele may induce the development of FSGS. Our findings suggest that haploinsufficiency of the WT1 could be responsible for the development of FSGS.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-Cho, Chuo-ku, Kobe 650-0017, Japan. iijima@med.kobe-u.ac.jp
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.forename: Tomonosuke
authors.initials: T
authors.lastname: Someya
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ito
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.forename: Michio
authors.initials: M
authors.lastname: Nagata
authors.forename: Koichi
authors.initials: K
authors.lastname: Kamei
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D005799:Genes, Dominant / Q000235:genetics; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D025721:WT1 Proteins