Identification of novel PAX6 mutations in two families with bilateral aniridia. Mutations in brief no. 167. Online.

We report two novel PAX6 mutations in aniridia patients of two Swiss pedigrees (We, Sc) which give rise to different phenotypes. An SSCP analysis of the PAX6 14 exons reveals electrophoretic mobility shifts exclusively in exons 5 and 12 of aniridia patients. As determined by bidirectional sequencing and restriction digest analysis, these shifts are caused by mono-allelic base transitions in exon 5 (c.547C-->T; R44X; We) and intron 12 (IVS12+5G-->A; Sc). Each mutation co-segregates with the trait in the affected family with complete penetrance. The Sc mutation in the splicing donor site of intron 12 may result in either intron inclusion or exon skipping, both giving rise to a truncated PAX6 protein which may retain a residual transactivating activity. In contrast, the We genetic alteration is a loss-of-function mutation leading to a more severe phenotype than that observed in the Sc pedigree.