A large novel deletion downstream of PAX6 gene in a Chinese family with ocular coloboma.

[aniridia]

The paired box gene 6 (PAX 6 ) is an essential transcription factor for eye formation . Genetic alterations in PAX 6 can lead to various ocular malformations including aniridia . The purpose of this study was to identify genetic defects as the underlying cause of familial ocular coloboma in a large Chinese family .After linkage analysis was carried out in this family , all exons of PAX 6 in the proband were sequenced by the Sanger sequencing technique . Then the genome of the proband was evaluated by a microarray-based comparative genomic hybridization (aCGH ). Quantitative real-time PCR was applied to verify the abnormal aCGH findings .All patients presented bilateral partial coloboma of iris , severe congenital nystagmus , hyperpresbyopia and congenital posterior polar cataracts . Two -point linkage analysis in the autosomal dominant family showed loss of heterozygosity at the D 11 S 914 locus . There was no pathogenic mutation in the exons of PAX 6 . The aCGH analysis revealed a 681 kb heterozygous deletion on chromosome 11 p 13 . Quantitative real-time PCR verified the deletion in the patients and further confirmed this deletion cosegregation with the ocular coloboma phenotype in the family .The 681 kb large deletion of chromosome 11 p 13 downstream of PAX 6 is the genetic cause of the familial ocular coloboma in this large Chinese family . aCGH should be applied if there is a negative result for the mutation detection of PAX 6 in patients with ocular coloboma .