New mutations in the PAX6 gene in patients with aniridia

Three novel mutations in the PAX6 gene have been found in patients with aniridia, adding to the data base of more than 200 different mutations in this gene.

Overall, aniridia has an incidence of about 1/80 000, and mutations in the PAX6 gene on chromosome 11p13 are responsible for about 80% of cases, both sporadic and familial. Normal eye development is highly susceptible to the degree of PAX6 expression. Haploinsufficiency causes aniridia and overexpresssion leads to microphthalmia.

The three new recently reported mutations were found in patients who were all heterozygous for their mutation. In one instance the mutation was found in three members of the same family—brother, sister and mother.

The PAX6 gene encodes a transcriptional regulator and produces two alternative splice isoforms that have distinct DNA binding specificities. Mutations are found throughout the gene so that extensive investigation is required in each case. The new mutations reported are all from unrelated families, and all probably lead to a truncated PAX6 protein. The first family carried a nonsense mutation in exon 8, another patient had a mutation in exon 10 and the third patient had a mutation which lead to aberrant mRNA splicing.

These findings indicate further the need for comprehensive genetic counselling in patients with aniridia in whom PAX6 mutations are detected.