Aniridia is an autosomal dominant eye anomaly caused by haploinsufficiency of the PAX6 gene, of which abnormalities include base alterations, position effects and deletions. When deletion involves its adjacent genes, i.e., those in the PAX6-WT1 critical region (WTCR), patients are predisposed to Wilms tumor. We studied 18 patients with aniridia, five of whom had chromosome deletion involving 11p13, two a translocation t(10;11)(p13;p13) or a der(14;21)(q10;q10)mat, and 11 had a normal karyotype. Fluorescence in situ hybridization (FISH) using four P1-derived artificial chromosome (PAC) clones located at WTCR was carried out in the 18 patients to identify a deletion extent. Of the 18 patients, eight had a deletion of WTCR: four had microscopic deletion and four a deletion of WTCR. Deleted region in one patient with a microscopic deletion was distal to the critical region. Four of the eight patients with a deletion encompassing WTCR developed Wilms tumor, and the other four did not (two were too young to be evaluated for the tumor development). The data in the present study, together with four similar previous works, indicate that of a total of 102 aniridia patients, 29 had a deletion spanning WTCR. Wilms tumor developed in 13 (45%) of the 29 patients, whereas patients without deletion in this region did not develop the tumor. In other words, aniridia patients with WT1 deletion run a high risk of developing Wilms tumor, and those without the deletion do not.
Copyright 2002 Wiley-Liss, Inc.