Molecular analysis of the PAX6 gene for congenital aniridia in the Korean population: Identification of four novel mutations

Purpose: To analyze the paired box gene 6 (PAX6) in Korean patients with congenital aniridia. Methods: Genomic DNA was isolated from peripheral blood leukocytes of 22 aniridia patients in 18 unrelated families. Polymerase chain reaction was performed for all 14 exons of PAX6 followed by bidirectional sequencing. Results: Fourteen different kinds of mutations were detected in 16 of 18 unrelated families (mutation detection rate: 88.9%), including four novel mutations; c. 658G>T (p.Glu220*), c. 464delG (p.Ser155Thrfs*52), c.87_90dupTGTA (p.Glu31Cysfs*26), and c.642A>C (p.Arg214Ser), among which the former three mutations induce premature termination of PAX6 protein translation. Approximately 92.9% of identified mutations lead to the premature termination of the protein resulting from 7 nonsense mutations (50.0%), 3 splicing errors (21.4%), 2 deletions (14.3%), and 1 insertion (7.1%). Conclusions: Most of the mutations identified in Korean aniridia patients lead to the premature truncation of the PAX6 protein, supporting that PAX6 protein haploinsufficiency causes the classic aniridia phenotype. We also found four novel PAX6 mutations associated with aniridia.