title: Submicroscopic deletions at the WAGR locus, revealed by nonradioactive in situ hybridization.
abstract: Fluorescence in situ hybridization (FISH) with biotin-labeled probes mapping to 11p13 has been used for the molecular analysis of deletions of the WAGR (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation) locus. We have detected a submicroscopic 11p13 deletion in a child with inherited aniridia who subsequently presented with Wilms tumor in a horseshoe kidney, only revealed at surgery. The mother, who has aniridia, was also found to carry a deletion including both the aniridia candidate gene (AN2) and the Wilms tumor predisposition gene (WT1). This is therefore a rare case of an inherited WAGR deletion. Wilms tumor has so far only been associated with sporadic de novo aniridia cases. We have shown that a cosmid probe for a candidate aniridia gene, homologous to the mouse Pax-6 gene, is deleted in cell lines from aniridia patients with previously characterized deletions at 11p13, while another cosmid marker mapping between two aniridia-associated translocation breakpoints (and hence a second candidate marker) is present on both chromosomes. These results support the Pax-6 homologue as a strong candidate for the AN2 gene. FISH with cosmid probes has proved to be a fast and reliable technique for the molecular analysis of deletions. It can be used with limited amounts of material and has strong potential for clinical applications.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: J A
authors.initials: JA
authors.lastname: Fantes
authors.forename: W A
authors.initials: WA
authors.lastname: Bickmore
authors.forename: J M
authors.initials: JM
authors.lastname: Fletcher
authors.forename: F
authors.initials: F
authors.lastname: Ballesta
authors.forename: I M
authors.initials: IM
authors.lastname: Hanson
authors.forename: V
authors.initials: V
authors.lastname: van Heyningen
mesh_terms: D000328:Adult; D015783:Aniridia / Q000235:genetics*; D002460:Cell Line; D002880:Chromosomes, Human, Pair 11; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D013577:Syndrome; D014564:Urogenital Abnormalities; D009396:Wilms Tumor / Q000235:genetics*