To explore the genotype-phenotype correlation among 3 pedigrees affected with congenital aniridia.

Clinical data and genomic DNA were collected and genetic variations were screened by whole-exome sequencing, with an emphasis on PAX6-related genes.Suspected variations were verified by Sanger sequencing and quantitative polymerase chain reaction (PCR). Written informed consent was obtained from the parents of each propositus prior to entering study cohort.This study protocol was approved by Ethic Committee of Henan Eye Hospital (No.HNEECKY-2017(6)).

Genetic analysis identified that a nonsense c. 949 C>T variation and an c. 141+ 1 G>T splicing variation of the PAX6 gene in two of the probands, while the remainder has carried a duplication in 11 p13 (chr11: 31531331-31827959) encompassing the PAX6 and ELP4 genes.Phenotype analysis showed that the probands carrying the nonsense and splicing variations had classical features including complete aniridia, macular hypoplasia, microcornea and nystagmus; the proband carrying the 11p13 duplication had microphthalmos, microcornea, macular dysplasia, iris dysgenesis, and nystagmus.

The 11p13 duplication involving the PAX6 gene may have caused over-expression of PAX6 gene, resulting in severe eye abnormalities including microphthalmos and microcornea, macular dysplasia and nystagmus.The relatively mild iris dysgenesis has distinguishing it from classical aniridia due to PAX6 haploinsufficiency.

Congenital aniridia; PAX6 gene; Copy number variation; Phenotype