Kokotas H, Petersen MB. Clinical and molecular aspects of aniridia.

Aniridia is a severe, congenital ocular malformation inherited in an autosomal‐dominant fashion with high penetrance and variable expression. Eye morphogenesis in humans involves a molecular genetic cascade in which a number of developmental genes interact in a highly organized process during the embryonic period to produce functional ocular structures. Among these genes, paired box gene 6 (PAX6) has an essential role as it encodes a phylogenetically conserved transcription factor almost universally employed for eye formation in animals with bilateral symmetry, despite widely different embryological origins. To direct eye development, PAX6 regulates the tissue‐specific expression of diverse molecules, hormones, and structural proteins. In humans, PAX6 is located in chromosome 11p13, and its mutations lead to a variety of hereditary ocular malformations of the anterior and posterior segment, among which aniridia and most probably foveal hypoplasia are the major signs. Aniridia occurs due to decreased dosage of the PAX6 gene and exists in both sporadic and familial forms. The mutations are scattered throughout the gene and the vast majority of those reported so far are nonsense mutations, frameshift mutations, or splicing errors that are predicted to cause pre‐mature truncation of the PAX6 protein, causing haploinsufficiency. Here we review the data regarding the mechanisms and the mutations that relate to aniridia.