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

The paired box gene 6 (PAX6) is an essential transcription factor for eye formation. Genetic alterations in PAX6 can lead to various ocular malformations including aniridia. The purpose of this study was to identify genetic defects as the underlying cause of familial coloboma of iris in a large Chinese family. After linkage analysis was carried out in this family, all exons of PAX6 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 D11S914 locus. There was no pathogenic mutation in the exons of PAX6. The aCGH analysis revealed a 681 kb heterozygous deletion on chromosome 11p13. Quantitative real-time PCR verified the deletion in the patients and further confirmed this deletion cosegregation with the coloboma of iris phenotype in the family. The 681 kb large deletion of chromosome 11p13 downstream of PAX6 is the genetic cause of the familial coloboma of ocular in this large Chinese family. aCGH should be applied if there is a negative result for the mutation detection of PAX6 in patients with aniridia. One Case sample and one control sample