Genetic clues uncovered

University of Edinburgh researchers have discovered a genetic mutation responsible for up to one in 10 cases of childhood blindness


The genetic underpinnings of ocular coloboma, a condition that is responsible for up to 10% of childhood blindness, have been investigated by University of Edinburgh researchers. 

As part of the study, published in Human Mutation, scientists worked with 12 families to study the DNA of children with ocular coloboma and their unaffected parents. 

Ocular coloboma can cause a portion of the iris to be missing, resulting in a distinctive keyhole-shaped pupil. There are few known genetic causes of the condition.

Researchers used whole exome screening to reveal mutations in 10 genes. Three of these mutations were linked to the molecule actin, which is responsible for several important cell functions.   

Gene sequencing was subsequently carried out on a further 380 people with coloboma, revealing that one of the mutations was a common thread across a number of those tested. 

The scientists then used gene editing technology to study what impact the mutation (an alteration in the gene ACTG1) had in mice. 

They discovered the altered gene had “severe effects” on the function of actin. 

The mutations are thought to influence actin’s stability and how it binds to other proteins, which could hinder development of the eye in the womb. 

The study was funded by the UK eye research charity, Fight for Sight. 

George McNamara, director of research, policy and innovation at Fight for Sight, told OT that sight loss as a result of coloboma in children could be “devastating.”

“Very little is known about the cause, and this study has helped advance our knowledge about the development of the eye,” he explained. 

“As the work progresses, we have the opportunity to come closer to understanding the causes of childhood sight loss,” Mr McNamara concluded.