Finding more of the genes that cause inherited blindness that starts in childhood

Research details

  • Type of funding: Project Grant
  • Grant Holder: Professor Tony Moore
  • Institute: UCL Institute of Ophthalmology
  • Region: London
  • Start date: January 2013
  • End Date: March 2016
  • Priority:
  • Eye Category:


Leber congenital amaurosis (LCA) is a severe inherited disorder that affects the light-sensitive part of the eye (the retina). It begins at birth or in the first months of life. Symptoms include poor vision and uncontrolled eye movements (nystagmus)

Faults in 15 genes are known to cause LCA but this only accounts for about 1 in 6 people with the condition. This means it’s likely that there are more genes to find. Faults in several of the known genes are also linked to another condition – early onset severe retinal dystrophy – which starts later in childhood than LCA and is less well understood.

There are no treatments for this group of inherited retinal disorders yet although a recent clinical trial for one form of LCA has led to some hope. Identifying the genes responsible for the remaining 4 in 10 people is essential for developing treatment and finding out which conditions are most likely to respond to treatment.

This project aims to identify new genes that cause the two conditions and to learn more about how they affect the retina. Results of this study will be shared with a national NHS service for molecular genetic diagnosis which offers genetic counselling and information to parents about what to expect in the long term.
  • Scientific summary

    Next generation sequencing in Leber congenital amaurosis and early onset severe retinal dystrophies

    This project aims to identify the genetic mutations underlying retinal disease in a large cohort of patients with Leber congenital amaurosis (LCA) and early onset severe retinal dystrophies (EOSRD). The cohort has already been recruited and has undergone detailed phenotyping. The samples have been analysed using array technology (Asper-Ophthalmics LCA chip) and Sanger sequencing of some known genes and no causative genes have yet been identified. This cohort is thus enriched for patients with mutations in novel genes.

    Known genes currently account for about 60% of cases of LCA and EOSRD. The team is utilising next generation sequencing (exome sequencing) to identify the causative genetic mutations. Novel genes identified using this approach will be screened in larger panels of patients with inherited retinal disease to identify further mutations.

    Once genotyping is complete they will be able to build up a comprehensive picture of the relationship between genotype and phenotype and most importantly identify which genetic forms of the disorder have sufficient retinal structure and function in infancy and early childhood to benefit from gene therapy or other forms of photoreceptor cell rescue. The team will, as a result of this research, also have identified a large group of well phenotyped patients of known genotype who will be available for any clinical trials.