Genetic Heterogeneity In Aniridia

Abstract

Purpose: : We present the genetic results of a case study supporting evidence for genetic heterogeneity in a family demonstrating aniridia

Methods: : Full genetic sequencing of the three family members regarding PAX6, SOX2, and OTX2 genes was carried out to evaluate the association with aniridia, microphthalmia, and anopthalmia.

Results: : The official notation for the PAX6 mutation observed in the child (GRADD) and his mother (GRAJA) is c.765+1_+2delGTinsCA. There is a strong splicing mutation at the splice donor site in intron 9 of PAX6. This will lead to a predicted premature protein termination, in some way that is not fully predictable. Non-causative variants were also identified in the father's (GRADA) PAX6 gene (c.327G>Ap.=(Glu109Glu) novel. This does not lead to a predicted protein change. This variant has not been seen before. In the mother's SOX2 gene: (c.453G>Ap.=(Ala151Ala) seen 1x. This is a nucleotide change that does not lead to a protein change and this variant has been seen once before. The child has not inherited either of these variants. A diagram of the family with the genomic changes is illustrated. We consider that the PAX6 changes in the mother and child account for their eye phenotype. We can report no causative gene change for the father's eye phenotype.

Conclusions: : Genetic heterogeneity exists and has been confirmed through genetic sequencing in a family demonstrating aniridia.

Keywords: iris • anterior chamber • anterior segment