Exome sequencing identifies existing and novel variants in a South African cohort presenting with anterior segment...

Anterior segment dysgenesis (ASD) defines a collection of congenital eye disorders that affect structures within the anterior segment of the eye. Mutations in genes that initiate and regulate the complex pathways involved in eye development can cause a spectrum of disorders such as ASD, congenital cataracts and corneal opacity. In South Africa, causes of ASD are poorly understood with few studies looking at the possible genetic basis for these disorders. In this study, we performed exome sequencing on a cohort of South African patients with ASD, focusing on a panel of genes known to regulate eye development pathways, including the PXDN gene which has recently been associated with ASD. We identified novel as well as established variants: specifically, we found a disease-causing variant in PAX6; variants that are likely to be pathogenic in GJA8, BCOR and EPHA2, as well as variants of uncertain significance in PXDN and LTBP2. In conclusion, this study is the first to show disease-causing variants in South African patients presenting with ASD, including the identification of novel variants and highlights the need to expand upon such studies in understudied populations.