Phenotype genotype correlation in autosomal dominant aniridia

Purpose. To investigate the relationship between specific mutations of the PAX6 gene and the ocular phenotype in families with dominant aniridia. Methods. Members of families with autosomal dominant aniridia were invited to take part in the study. Blood was taken for molecular genetic analysis from affected and unaffected family members. Standard molecular genetic techniques were used to identify mutations in each of the 14 exons of the PAX6 gene. In seven families a specific mutation was identified. Twenty-nine affected members from these families agreed to undergo full ophthalmic assessment. Results. The majority of the mutations of the PAX6 gene identified resulted in stop codons and an inactive protein product. A wide range of phenotype was observed including anterior polar cataract, lens subluxation, glaucoma and corneal surface disease. In two families there was associated ptosis and in one family some affected members had dental anomalies. Conclusion. In most families with dominant aniridia the mutation in the PAX6 gene results in an inactive protein. Although some differences (for example, the presence of ptosis and dental anomalies) could be demonstrated with different mutations there was considerable overlap in the other phenotypes.