Novel and De-novo Truncating PAX6 Mutations and Ocular Phenotypes in Thai Aniridia Patients

Abstract

Purpose: To describe the ophthalmic findings and mutation analyses of the PAX6 gene in Thai aniridia patients. Methods: Ten patients from six unrelated families underwent a comprehensive ophthalmic examination. Mutations in the PAX6 gene were screened by single-strand conformational polymorphism (SSCP) and direct DNA sequencing of the SSCP variants. Results: Seven patients developed cataracts and six developed glaucoma. Mutation analysis demonstrated four different truncating mutations, two of which were de novo. These included one novel insertion/deletion mutation (c.474del12insGA in exon 5) and three nonsense mutations. R203X and R240X are common recurrent mutations, while Q277X in exon 10 is novel. All mutations resulted in loss of function of the PAX6 protein. Conclusion: Our data confirm inter- and intrafamilial variable phenotypic manifestations of which the underlying mechanisms may be haploinsufficiency or dominant-negative mutation.

keywords:

• Aniridia
• PAX6
• ectopia lentis
• foveal hypoplasia
• juvenile onset glaucoma