A genetic mutation that contributes to sight loss in children has been identified by scientists at The Roslin Institute.
Ocular coloboma causes part of the iris of the eye to be missing at birth and accounts for up to 10% of all childhood blindness. New findings shed light on its causes and help to explain how genes contribute to the development of the eye.
George McNamara from the UK charity Fight for Sight said: “Sight loss in coloboma in children can be devastating. As this work progresses, we have the opportunity to come closer to understanding the causes.”
A research team – led by Dr Joe Rainger at The Roslin Institute – worked with 12 families, studying the DNA of children with coloboma and their unaffected parents. Using whole exome sequencing, the scientists revealed mutations in ten genes, three of which were linked to the activity of one molecule: actin.
Actin is important for a number of vital cell functions, including maintenance of the cytoskeleton, which defines cell shape and structure.
Targeted gene sequencing was then carried out on a further 380 people with coloboma. This showed that one of the mutations – a specific alteration in the gene ACTG1 – recurred across a number of those tested.
The scientists edited this ACTG1 mutation into a line of mice using cutting-edge CRISPR/Cas9 gene-editing technology and found that it had severe effects on the function of actin. The newly-identified mutations are thought to affect how actin binds to other proteins and on actin stability, which could severely affect development of the eye in the womb.
Dr Joe Rainger explains: “Coloboma can have profound effects on visual ability, but it is very variable and therefore likely to be caused by a number of genes. Our work adds knowledge to our understanding of its onset as well as the importance of actin to eye development.”
The work – published in the journal Human Mutation – was carried out at the University of Edinburgh’s Institute for Genetics and Molecular Medicine and The Roslin Institute. The study was funded by eye research charity Fight for Sight.