These disorders include congenital cataract anterior segment dysgenesis, childhood glaucoma and whole of eye disorders such as microphthalmia. We aim to discover the underlying disease genes and the functions of the proteins they encode.
We use next-generation sequencing techniques and genomic investigations to pinpoint disease genes. The functions of the disease genes are investigated using stem cell and mouse model systems, which provide a passage to development of novel treatment strategies.
The Eye Genetics Research Group uses whole genome approaches in human patients to identify underlying disease genes in eye and other developmental diseases. Cell based and animal model studies are undertaken to understand how the disease genes lead to the particular abnormality. We are also investigating new ways to target specific eye cells and correct gene mistakes for development of novel treatments for these conditions.
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.