Comparison between aniridia with and without PAX6 mutations: clinical and molecular analysis in 14 Korean patients with aniridia.

PURPOSE: To describe clinical and molecular characteristics of Korean patients with aniridia and to compare the clinical phenotype between those having an identifiable PAX6 mutation and those not.

DESIGN: Comparative case series.

PARTICIPANTS: A total of 14 Korean patients from 10 families with aniridia.

METHODS: Complete ophthalmologic examinations were performed for all patients. PAX6 analysis included direct sequencing of all coding regions and multiplex ligation-dependent probe amplification (MLPA) to detect large deletions when the sequencing was negative. If the PAX6 analysis failed to reveal any identifiable mutations, genomic copy number variation analysis via array comparative genomic hybridization (CGH) and candidate gene PITX3 and FOXE3 sequencing were then performed.

MAIN OUTCOME MEASURES: Severity of ocular abnormalities and genetic findings.

RESULTS: Sequencing of PAX6 exhibited 5 different heterozygous mutations in 8 patients from 5 families; 2 (p.Ser43Phe, IVS8-9C>G) were novel, and 3 (p.Arg208Trp, p.Arg317X, and p.X423L) have been previously reported. Among the remaining 6 patients in whom the PAX6 sequencing was negative, MLPA identified large deletions in 2 sporadic patients. However, the array CGH and candidate gene sequencing found no genomic or genetic abnormalities. The mutation detection rate was therefore 70%. Patients harboring an identifiable mutation in PAX6 had either a severe or a mild variant phenotype depending on the type of mutations. Likewise, among patients without an identifiable PAX6 mutation, their phenotypes varied widely from severe to very mild.

CONCLUSIONS: This study adds 2 novel PAX6 mutations to those previously reported, providing further evidence for genetic and phenotypic heterogeneity in aniridic ocular malformation. There was no difference in the clinical phenotype between patients with and without detectable mutations in the PAX6 gene. The wide variability of ocular phenotype regardless of the presence or absence of PAX6 mutations calls for a further appreciation of the complexity in the molecular diagnosis of aniridia and suggests that this ocular malformation may be better regarded as a group of heterogeneous disorders, rather than a single disease entity, associated with mutations in PAX6 and/or other genes located elsewhere in the human genome.

FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.