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Abstract #18546 Published in IGR 3-3
Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia
Gronskov K; Olsen JH; Sand A; Pedersen W; Carlsen N; Bak Jylling AM; Lyngbye T; Brondum-Nielsen K; Rosenberg THuman Genetics 2001; 109: 11-18
Aniridia is a severe eye disease characterized by iris hypoplasia; both sporadic cases and familial cases with an autosomal dominant inheritance exist. Mutations in the PAX6 gene have been shown to be the genetic cause of the disease. Some of the sporadic cases are caused by large chromosomal deletions, some of which also include the Wilms tumor gene (WAGR syndrome), resulting in an increased risk of developing Wilms tumor. Based on the unique registration of both cancer and aniridia cases in Denmark, the authors have made the most accurate risk estimate to date for Wilms tumor in sporadic aniridia. They found that patients with sporadic aniridia have a relative risk of 67 (confidence interval: 8.1-241) of developing Wilms tumor. Among patients investigated for mutations, Wilms tumor developed in only two patients of five with the Wilms tumor gene (WT1) deleted. None of the patients with smaller chromosomal deletions or intragenic mutations were found to develop Wilms tumor. These observations suggest a smaller risk for Wilms tumor than previous estimates, and that tumor development requires deletion of WT1. The authors report a strategy for the mutational analysis of aniridia cases resulting in the detection of mutations in 68% of sporadic cases and 89% of familial cases. They also report four novel mutations in PAX6, and furthermore, they have discovered a new alternatively spliced form of PAX6.
Dr K. Gronskov, Department of Medical Genetics, The John F. Kennedy Institute, Gl. Landevej 7, DK2600 Glostrup, Denmark. kag@kennedy.dk
Classification:
1.2 Population genetics (Part of: 1 General aspects)