Two novel PAX6 mutations identified in northeastern Chinese patients with aniridia.

PURPOSE The PAX6 gene encodes a transcriptional regulator involved in oculogenesis and other developmental processes such as aniridia, a congenital condition characterized by the underdevelopment of the eye's iris. Aniridia may be broadly divided into hereditary and sporadic forms. The function of the PAX6 gene in these two forms of aniridia is still poorly defined. Therefore, we carried out a mutation analysis of the PAX6 gene in northeastern Chinese families with aniridia to identify the role of the PAX6 gene in hereditary aniridia. METHODS Five aniridia patients from two northeastern Chinese families (Family 1 and Family 2) underwent full ophthalmologic examinations. Genomic DNA was prepared from venous leukocytes from these five patients, 10 non-carriers in these two families, as well as 100 healthy normal controls. The coding regions of PAX6 were analyzed by PCR amplification, direct sequencing and allele-specific cloning sequencing. RESULTS We identified two novel PAX6 mutations. The first is a 9 base pair (bp) deletion in exon 5 (c.483del9) that makes a PAX6 protein with de novo in-frame deletions of aspartic acid, isoleucine, and serine at the amino acid codon positions 41-43. The second is a heterozygous mutation (IVS10+1G>A) located at the boundary of exon 10 and intron 10. CONCLUSIONS We identified two novel PAX6 mutations in familial aniridia from northeastern China, an ethnic group that is not well-studied. The genetic analysis confirms that these two novel mutations in PAX6 are capable of causing the classic aniridia phenotype. Therefore, by studying human familial aniridia cases, we demonstrated that PAX6 plays a role in hereditary aniridia.