Autosomal dominant aniridia is the result of PAX6 (a transcription regulator gene) dysfunction. In the majority of cases there are mutations in the PAX6 gene itself as in AN1. There are reports, however, of familial aniridia in which direct PAX6 mutations have been excluded. Two additional forms of aniridia in which there are alterations in genes that modulate the expression of PAX6 have been reported. AN2 described here with mutations in ELP4 (a nucleotide variant within an intron of the ELP4 gene (11p13) located distal to the 3-prime end of the PAX6 gene, plus AN3 (617142) with mutations in TRIM44. Both ELP4 and TRIM44 are regulators of the PAX6 transcription gene.
Aniridia 2 has been reported in one patient with a nucleotide variant within an intron of the ELP4 gene (11p13) located distal to the 3-prime end of the PAX6 gene. The gene product is a cis-regulatory enhancer.
Other evidence for aniridia resulting from regulatory modification of PAX6 gene function comes from families in which there are structural alterations such as deletions in chromosome 11, downstream of the PAX6 gene location.