PurposeTo reveal the underlying genetic defect in two four-generation Chinese families with
aniridia and explore the pathologic mechanism.MethodsFull ophthalmic examinations were performed in two families with
aniridia. The PAX6 gene was directly sequenced in patients of two families, and the detected variants were screened in unaffected family members and two hundred unrelated healthy controls. Real-time quantitative PCR was used to explore pathologic mechanisms of the two variants.ResultsAniridia,
cataract, and oscillatory nystagmus were observed in patients of the two families. In addition, we observed
corneal opacity and microphthalmus in family 1, and
strabismus, left
ectopia lentis, microphthalmus, and microcornea in family 2. Sanger sequencing detected a novel 1-bp duplication (c.50dupA) in family 1 and a novel 2-bp splice site deletion (c.765+1_765+2delGT) in family 2. Sequencing of
cDNA indicated skipping of exon 9 caused by the splice site deletion, being predicted to cause a
premature stop codon, as well as the duplication. The PAX6
mRNA significantly lower in patients with
aniridia than in unaffected family members in both families, suggesting that the duplication and splice site deletion caused nonsense-mediated mRNA decay.ConclusionsOur study identified two novel PAX6 variants in two families with
aniridia and revealed the pathogenicity of the variants; this would expand the variant spectrum of PAX6 and help us better understand the molecular basis of
aniridia, thus facilitating genetic counseling.