Cataract anterior segment and glaucoma

Using exome sequencing, all of the coding regions of an individual’s 23,000 genes are sequenced in one single test. We have successfully applied this technique to investigate disease genes that cause cataract/microcornea, Peters anomaly and microphthalmia/coloboma. This work was accepted for publication in the European Journal of Human Genetics, and the technique is now being applied to patients with retinal dystrophies.

Targeted NGS is a new capture technique that was devised to select the coding regions of more than 50 genes known to be critical in the lens and anterior segment of the eye. We applied this to patients with cataract and microcornea/microphthalmia, and preliminary results show it has a disease identification success rate similar to that of exome sequencing. This finding has potential to reduce the cost of diagnostic testing. We are collaborating with The Children’s Hospital at Westmead to translate  findings into new and accessible diagnostic tests for patients with genetic eye disorders.

We have identified a number of novel candidate disease genes from exome sequencing and the investigation of patients with eye diseases and structural genomic variation.

Anophthalmia and microphthalmia are severe debilitating conditions, and while some disease genes are known, they only contribute to a small number of cases.

Our exome sequencing work in patients with this group of disorders suggests that variants in a number of genes may contribute to the disorder in any one particular patient.

Our study of a large family has identified a novel contributor disease gene which is important in the Wnt signalling pathway.  Study of further patients is underway to examine the wider impact of variation in this gene in other patients and families.