Research team discovers gene critical for human eye, brain and limb development

Oxford Brookes UniversityAug 21 2019

An international collaboration led by a team at Oxford Brookes University has identified an important new gene which could open up new doors for research and developing new therapies.

The team has discovered that the gene FBXW11 drives the development of key structures, including the brain, eyes, hands and feet. Individuals with alterations of this gene showed developmental delay, brain and eye anomalies, and contractures affecting their fingers and toes.  

With around 1 in 3,500 children born with one or both of their eyes not fully developed, identifying which genes are related to eye development is key for better diagnosis and treatment.

Nicola Ragge, Professor in Medical Genetics at Oxford Brookes, and a consultant clinical geneticist at Birmingham Women’s and Children’s Foundation Hospital Trust, who led the study - published in The American Journal of Human Genetics- said:

This is an exciting and important breakthrough that has identified a new gene important in human eye development that also is involved in developing structures in the brain and limb.

This gene appears to be at the cornerstone of three different development pathways and has significantly enhanced our understanding of the networks involved in human eye, brain and limb development. They plan to use this foundation to benefit patients and their families by improving genetic testing and exploring therapeutic avenues in the future”.

The team demonstrated that this gene is switched on in human eye, brain and limb development at an early stage of an embryo’s growth.  In order to understand the importance of FBXW11 during embryonic development, they studied this gene further in zebrafish. Zebrafish provide a very good model for genetic study, and the team found that when they switched off FBXW11 off in these fish, it led to fascinating results. These fish began to develop similar physical features to those seen in some patients, including smaller eyes and abnormal fins (equivalent to limb in humans).

The team also mapped the gene alterations in their patients and demonstrated that their patients all had DNA alterations in similar parts of the gene, although they had varied clinical features. The gene alterations affected the ‘propeller’ structure of the protein produced by the gene, which is predicted to change its interactions with other important proteins downstream.

This displays the complex interaction of genes and other factors in human development that lead to impacts on human health. This greater understanding of FBXW11 could also shed light on a number of related conditions.

Now that the gene has been identified, scientists are excited for the new research this will prompt across the world. As more studies are undertaken to build on these findings, our knowledge of these developmental conditions and possibly our future ability to treat this gene will grow.

With therapeutic trials already underway for treatment for some genetic conditions, including those affecting the eye, this represents the next step towards new genomic medicine approaches that could in future be of great help to newborn children affected by developmental disorders related to this gene and its partners.