Researchers identify previously unknown irregularities in Stargardts associated gene

May 6, 2020

A large group of collaborators, led by Fighting Blindness funded researcher Prof Frans Cremers, and Dr Claire Dhaenen, at the Department of Human Genetics in Nijmegen, the Netherlands have identified the changes in the ABCA4 gene responsible for Stargardts disease in 448 people.

The research was made possible through the collaboration of 75 scientists, several of which we proudly fund, across 21 countries around the world. Irish researchers based at Trinity College Dublin were part of this collaborative effort and Irish patient samples were used in this study to make these breakthrough discoveries.

In their research paper, recently published in the journal Genetics in Medicine, the team describe their cost-effective methods that allowed them to sequence the entire ABCA4 gene in more than 1000 samples. This new method replaced conventional genetic testing which analyses only certain parts of the gene, the region that is responsible for the production of the ABCA4 protein, for example.

Incredibly, the team of researchers identified 105 previously unknown changes (sometimes termed mutations) following sequencing of the entire gene. These irregularities affect normal ABCA4 gene function resulting in central vision defects and identification of these changes has significantly improved the knowledge-base of the processes through which Stargardts occurs.

In addition to changes in the gene, 16 new deletions (loss of parts of the gene), were also identified. These new findings were found in 27% of 448 genetically resolved cases, which researchers believe indicates a high number of these genetic changes are associated with Stargardts disease developing.

It is thanks to the generosity of our members and the general public that we are able to fund this vital research.

This full research study has now been published in Genetics of Medicine.

Among the Irish effort in this study was Fighting Blindness funded PhD student Laura Whelan, “As part of this momentous study, I worked alongside an international team to detect changes in DNA that may cause Stargardt disease. I gained invaluable skills that are now being used by our research team in TCD genetics and could also be applied to other forms of visual impairment in Ireland in the future.

“Affordable DNA sequencing technology used here to analyze one gene implicated in Stargardt disease will now be used soon to sequence more than 200 genes involved in inherited blindness, having a positive impact for many.”

Meet Prof Cremers and what attracted him to genetic retinal research.