Submicroscopic deletions at the WAGR locus, revealed by nonradioactive in situ hybridization.
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.
Fantes
J A
JA
MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom.
Bickmore
W A
WA
Fletcher
J M
JM
Ballesta
F
F
Hanson
I M
IM
van Heyningen
V
V
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*