News items Women more likely to develop mild variant Stargardt's disease

24 May 2024

In the mild form of Stargardt's disease, a hereditary eye disease, women are more likely to have vision problems than men. This emerges from research on which Stéphanie Cornelis is receiving her PhD from the Radboudumc. This knowledge is important for the prognosis of the disease and more individualized treatment.

Stargardt's disease is an inherited disorder that affects the retina (yellow spot/macula). The disease results from errors (mutations) in the ABCA4 gene, and it is the most common form of vision loss. It affects about 1 in 10,000 people. Depending on the mutation in the gene, the disease can be severe and lead to blindness at an early age. Other mutations, on the other hand, are mild and do not lead to vision problems until somewhat later in life or even at all. Because each parent can pass on a mutation in the ABCA4 gene - you need a mutation from both parents to actually develop the disease - there is enormous variation in the timing and severity of the disease. No therapy is currently available.


Early and advanced stage Stargardt's disease

Two thousand mutations weigh in

"Indeed, we see an enormous amount of variation in Stargardt's disease," says researcher Stéphanie Cornelis. "The ABCA4 gene consists of six thousand nucleotides, of six thousand genetic letters. In my research, I listed over two thousand mutations in individuals with Stargardt that could contribute to the disease. I then mapped whether, and if so, exactly how much those individual mutations contribute to the disease. On that basis, for people with Stargardt disease, you can now also make a fairly reliable estimate of the likelihood of the disease in children. That’s between two to four percent."


Mild form more common in women

Yet the research shows that not only genetic factors determine the severity and onset of the disease. Other factors also play a role. Cornelis: "In different patient groups from the Netherlands, France and England, we saw a remarkable difference especially in the mild forms of Stargardt's disease. In that mild form, the disease occurs half as often in women as in men. This is a large difference that cannot be traced to genetic mutations. So apparently sex or gender also play a role."


Protect or promote

Why do these differences between women and men play out so clearly precisely in the mild variant? "We may not see this influence in the severe forms because they develop anyway, even without any other factors," says Cornelis. "Especially in the mild forms, other factors may possibly still exert some influence. Whether those are protective factors in the male or promoting factors that in the female; we don't know. Nor do we know whether they are hormonal, immunological or yet other influences. Further research should clarify that. In any case, we can better tailor care to the individual person with Stargardt's disease because we have a better picture of the genetic and gender differences."


Thesis Stéphanie Cornelis: Understanding ABCA4 variant effects in Stargardt disease. Towards personalized healthcare.

Friday, May 24 at 10:30 am, Promotor Frans Cremers, co-supervisor Susanne Roosing

More information

Pieter Lomans


Related news items

Nijmegen researchers find new genetic cause bubble boy disease SCID Genetic new born screening SCID can be further refined

19 March 2024

Researchers from Nijmegen and Newcastle discovered a new genetic mutation leading to severe combined immune deficiency disorder (SCID). It’s the first time a mutation in the proteasome, a molecular shredder, has been linked to this serious disease.

read more

OnePlanet Research Center celebrates five-year anniversary with event 'Gelderland innovations with global impact'

7 March 2024

The OnePlanet Research Center innovation center is five years old and is celebrating with an anniversary event on April 3, 2024 at Industriepark Kleefse Waard in Arnhem.

read more

Radboudumc participates in HiFi Solves, a Global Consortium of Clinical Genomics Research Leaders Aim to Share Best Practices and Increase the Understanding of Genetic Disease

22 November 2023

HiFi Solves, a Global Consortium of Clinical Genomics Research Leaders including Radboudumc, is going to start

read more

New Nijmegen method reveals hidden genetic variations Valuable data mining in the dark corners of the exome now possible worldwide

1 November 2023

Many hidden genetic variations can be detected with Chameleolyser, a new method developed in Nijmegen.

read more