Genetic mutation linked to childhood blindness discovered

The mutation was identified in patients with ocular coloboma, a disease which causes part of the eye to be missing at birth, and researchers say the findings shed light on its causes and help explain how genes contribute to eye development.“Sight loss due to coloboma in children can be devastating. As this work progresses, we have the opportunity to come closer to understanding the causes of childhood sight loss,” Mr George McNamara, a director of a charity that helped fund the research said.{{quote-A:R-W:450-I:2-Q:““Sight loss due to coloboma in children can be devastating. As this work progresses, we have the opportunity to come closer to understanding the causes of childhood sight loss,” -WHO:Mr George McNamara, Biomedical Consultant Innovator}}The team used a state-of-the-art genetic screening technique called whole exome sequencing (WES) to reveal mutations in 10 genes, three of which were linked to the activity of one molecule. The molecule – actin – is important to a number of vital cell functions, including maintenance of the cytoskeleton, which defines cell shape and structure.In the case of ocular coloboma, which accounts for up to 10% of all childhood blindness, the genetic mutation causes a distinctive keyhole-shaped pupil and commonly results in a missing segment in the iris. “Our work adds knowledge to our understanding of its onset as well as the importance of actin to eye development,” study lead Dr Joe Rainger said.The research team worked with 12 families of patients diagnosed with coloboma by studying the DNA of the patients and their unaffected parents.The process was then followed by targeted gene sequencing on 380 patients with coloboma, which showed that one of the mutations – a specific alteration in the gene ACTG1 – recurred across a number of those tested.Using CRISPR/Cas9 gene editing technology, the team edited the ACTG1 mutated gene in test mice and found it severely affected the function of actin.According to the researchers, the mutations were believed to affect actin stability and how it binds to other proteins, thus affecting eye development in the mother’s womb.