Gene study sheds light on causes of childhood sight loss

May 18, 2017, University of Edinburgh
This stylistic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). The chromosome is X-shaped because it is dividing. Introns are regions often found in eukaryote genes that are removed in the splicing process (after the DNA is transcribed into RNA): Only the exons encode the protein. The diagram labels a region of only 55 or so bases as a gene. In reality, most genes are hundreds of times longer. Credit: Thomas Splettstoesser/Wikipedia/CC BY-SA 4.0

A genetic mutation that contributes to sight loss in children has been identified by scientists.

The mutation was identified in patients with a disease known as ocular coloboma, which causes part of the eye to be missing at birth.

The findings shed light on its causes and help to explain how contribute to development of the eye, researchers say.

Ocular coloboma accounts for up to 10 per cent of all . It can cause a distinctive keyhole-shaped pupil as it commonly results in a missing segment in the iris, the coloured part of the eye.

Few genetic causes have so far been found to explain the cause of coloboma.

The research team—lead by the University of Edinburgh—worked with 12 families, studying the DNA of children with coloboma and their unaffected parents.

Using state-of-the-art genetic screening—known as whole exome sequencing—the scientists revealed mutations in 10 genes, three of which were linked to activity of one molecule.

The molecule—known as actin—is important to 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 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, scientists say.

Dr Joe Rainger, Fight for Sight Early Career Investigator Fellow at the University of Edinburgh's Roslin Institute and Royal (Dick) School of Veterinary Studies, said: "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 to eye development."

Explore further: Researchers identify gene mutation that can cause key-hole shape defect in eye

More information: Joe Rainger et al, A recurrentmutation incauses isolated ocular coloboma, Human Mutation (2017). DOI: 10.1002/humu.23246

Related Stories

Researchers identify gene mutation that can cause key-hole shape defect in eye

June 23, 2015
A scientific collaboration, involving the Manchester Centre for Genomic Medicine (MCGM) at Saint Mary's Hospital, UK, and the Telethon Institute of Genetics and Medicine (TIGEM) in Naples, Italy, has pinpointed the genetic ...

Cause of fatal childhood disorder revealed in gene study

April 14, 2017
A gene involved in brain development that can lead to severe disability and infant death has been identified by scientists.

Mutations in CWC27 result in a spectrum of developmental conditions

March 10, 2017
An international team of researchers has discovered that mutations in the human gene CWC27 result in a spectrum of clinical conditions that include retinal degeneration and problems with craniofacial and skeletal development. ...

Causative gene for sensorineural hearing loss identified

October 6, 2016
A causative gene for a highly common type of hearing loss (sensorineural hearing loss, or SNHL) has been identified by a group of Japanese researchers, who successfully replicated the condition using a transgenic mouse. This ...

Babies born with no eyes: Scientists identify genetic cause

December 12, 2011
Scientists at University College Dublin, Ireland, have identified a genetic alteration which causes a child to be born with no eyes – a condition called anophthalmia.

Study finds new genes that cause Baraitser-Winter syndrome, a brain malformation

February 29, 2012
Scientists from Seattle Children's Research Institute and the University of Washington, in collaboration with the Genomic Disorders Group Nijmegen in the Netherlands, have identified two new genes that cause Baraitser-Winter ...

Recommended for you

Scientists identify critical cancer immunity genes using new genetic barcoding technology

October 20, 2018
Scientists at Mount Sinai have developed a novel technology for simultaneously analyzing the functions of hundreds of genes with resolution reaching the single cell level. The technology relies on a barcoding approach using ...

A single missing gene leads to miscarriage

October 19, 2018
A single gene from the mother plays such a crucial role in the development of the placenta that its dysfunction leads to miscarriages. Researchers from the Medical Faculty of Ruhr-Universität Bochum (RUB) have observed this ...

Making gene therapy delivery safer and more efficient

October 18, 2018
Viral vectors used to deliver gene therapies undergo spontaneous changes during manufacturing which affects their structure and function, found researchers from the Perelman School of Medicine at the University of Pennsylvania ...

Student develops microfluidics device to help scientists identify early genetic markers of cancer

October 16, 2018
As anyone who has played "Where's Waldo" knows, searching for a single item in a landscape filled with a mélange of characters and objects can be a challenge. Chrissy O'Keefe, a Ph.D. student in the Department of Biomedical ...

Researchers use brain cells in a dish to study genetic origins of schizophrenia

October 16, 2018
A study in Biological Psychiatry has established a new analytical method for investigating the complex genetic origins of mental illnesses using brain cells that are grown in a dish from human embryonic stem cells. Researchers ...

Why heart contractions are weaker in those with hypertrophic cardiomyopathy

October 16, 2018
When a young athlete suddenly dies of a heart attack, chances are high that they suffer from familial hypertrophic cardiomyopathy (HCM). Itis the most common genetic heart disease in the US and affects an estimated 1 in 500 ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.