Identification of novel genetic causes of ocular maldevelopment

Summary

When the eye fails to form properly in early pregnancy due to genetic changes, this leads to several birth eye defects e.g. microphthalmia (underdeveloped small eye), anophthalmia (complete absence of the eye), ocular coloboma (cleft through eye), anterior segment dysgenesis (front part of the eye is disorganised with clouding of the surface of the eye, high pressure and/or clouding of the lens).

These conditions are responsible for >30% of severe visual impairment in children, and > 60% patients also have other organs of the body involved e.g. heart and kidney defects, hearing loss, epilepsy and obesity. Overall 25% of patients receive a genetic diagnosis after testing; this prevents patients accessing the correct specialists, receiving informed genetic counselling, family planning advice and entry into clinical trials. There are a significant number of genes and disease mechanisms still to be discovered.

Assessing the pattern of genes working in this group of patients, recalled from the Microphthalmia, Anophthalmia and Ocular Coloboma (MAC) cohort at the Rare Diseases BioResource, will enable us to identify new genes and genetic pathways playing a role in eye development and underlying disease mechanisms. We can now grow early eyes in a dish from a patient’s skin or blood sample, so we will be able to confirm any new genes in these exciting models.

This study is part of our Rare Diseases RNA Phenotyping Project. Each participating study in the project is included in a collection hosted on our main studies page.