A FISH approach to defining the extent and possible clinical significance of deletions at the WAGR locus.

Abstract

Nineteen patients were analysed by fluorescence in situ hybridisation (FISH) with selected lIpl3 markers. They were examined because they had either isolated sporadic or familial aniridia, or aniridia with one or more of the WAGR (Wilms' tumour, aniridia, genital anomalies, and mental retardation) syndrome anomalies. The FISH markers from distal lIpl3 were cosmids F02121, PAX6 (aniridia), DllS324, and WT1 (Wilms' tumour predisposition). Two of the patients with isolated aniridia were abnormal, one with an apparently balanced reciprocal 7;11 translocation and an 1ipi3 breakpoint, which by FISH was shown to be -30 kb distal to the aniridia (PAX6) gene, and the other had a submicroscopic deletion involving part of PAX6 that extended distally for -245 kb. Two patients with aniridia together with other WAGR malformations had deletions involving all four cosmids. One case with aniridia associated with developmental and growth delay had a deletion including F02121 and PAX6 but not DI1S324 and WT1, while in a further case the deletion included all four test cosmids. These studies show that a combined conventional and molecular cytogenetic approach to patients presenting with aniridia is a useful method for differentiating between those with deletions extending into and including WT1 and therefore between those with high and low risks of developing Wilms' tumour.

Analysis of Pax6 Contiguous Gene Deletions in the Mouse, Mus musculus, Identifies Regions Distinct from Pax6 Responsible for Extreme Small-Eye and Belly-Spotting Phenotypes

“…An extensive series of PAX6 intragenic mutations has been identified in humans (http://pax6.hgu.mrc.ac.uk) and a number of contiguous gene deletions encompassing the PAX6 region have been characterized (van Heyningen et al 1985;Fantes et al 1992;Drechsler et al 1994;Crolla et al 1997;Chao et al 2000;Grønskov et al 2001;Crolla and van Heyningen 2002;Robinson et al 2008). We are unaware of any studies which have compared the extent of the eye abnormalities expressed by carriers of deletions vs. intragenic mutant alleles.…”

Controversies and advances in the management of Wilms' tumour

“…For example, in sporadic aniridia, high resolution karyotyping using probes for the contiguous PAX6, calmodulin, and WT1 genes on 11p13 can distinguish those children whose aniridia is a result of mutation confined to PAX6 and therefore not requiring screening from those with a more extensive deletion involving the WT1 gene. 21 Similarly, children with early onset nephrotic syndrome involving diffuse mesangial sclerosis, even without ambiguous genitalia, are likely to harbour a constitutional WT1 mutation and hence carry an increased risk of Wilms' tumour. 9 In aniridia and BWS, where the risk of Wilms' tumour is of the order of 10-30%, it is a generally held view that some sort of screening programme is justified.…”

11p13 Deletion Syndrome: First Case in Morocco Detected by FISH

“…Clinical presentation is variable and may, but must not include aniridia. Such cases are suggested to have an incidence of 1/50,000 to1/100,000 [8,9]. In cases with aniridia, the PAX6 gene is mutated or deleted, which encodes a transcriptional regulator and involved in ocular morphogenesis.…”