A world-first global survey has revealed the full impact X-linked inherited retinal diseases (IRDs) have on female carriers, and the shortfall of support they need.
The study performed by Sena Gocuk, Clinical Research Coordinator at the Centre for Eye Research Australia and PhD student at the University of Melbourne, is the first time a global survey of female carriers of X-linked IRDs has been undertaken.
Her research has shown that female carriers of X-linked IRDs experience feelings of guilt, concern and anxiety for potentially passing down the disease-causing gene to future generations, while also showing an interest in participating in research for future treatments.
"Inherited retinal disease carriers haven't previously been tested for their knowledge, opinions, emotions or experiences about being told they have the condition," says Gocuk.
"This is the first study looking at carriers of X-linked IRDs, and the first comparing different regions from a global perspective."
X-linked conditions
X-linked IRDs are associated with genes in the X-chromosome, which is typically passed down to a person by their parents.
For males who have one X-chromosome, the genetic mutation causes full expression of the condition.
However, females have two X-chromosomes. Thie means that female carriers can have one chromosome with the genetic mutation and one healthy version. Generally, this means that the gene mutation is not fully expressed - meaning the condition doesn't always cause visual symptoms.
Historically, it was believed that most female carriers of X-linked IRDs would not have vision problems, but we now know that this is not the case.
"Female carriers actually present with a spectrum of retinal disease - some have significant vision loss or even legal blindness, while in others the condition is so mild, they may not ever realise they have it," says Gocuk.
"In these cases, it can come as a shock when they find out they are a carrier for the disease only after having an affected child."
Most carriers identified with feelings of guilt (70%), concern (91%), and anxiety (88%) for their child, but very few in the survey reported receiving psychological counselling or family planning advice.
"Genetic testing and genetic counselling can really help guide carriers through family planning, so they can make informed decisions."
"We also found that 78 percent of respondents believed gene therapy should be available for female carriers of X-linked IRDs, showing the impact these conditions have on individuals and their motivation to save their sight," says Gocuk.
Her research also highlighted some important differences between countries, particularly when people found out they were a carrier.
"In the US, women generally found out in their 20s they were a carrier, whereas Australia women were in their late 30s.
"In terms of starting a family, the younger you find out the better, so that you can plan ahead and make informed decisions."
Award winning work
Gocuk was recently awarded the Dean's Award for Excellence in Graduate Research by the University of Melbourne Faculty of Medicine, Dentistry and Health Sciences, for her research in 2023.
The award recognises outstanding graduate research in the Faculty, and is a highly prestigious accolade of Gocuk's work and impact.
Gocuk hopes her work may help lay the groundwork for providing carriers of X-linked IRDs more support and opportunities, including potential therapeutic treatment trials, such as gene therapy.
"While not every carrier will be eligible for treatment, this research shows many would certainly consider being involved and might benefit from future therapies."
Read the research
Gocuk et al, Perspectives of carriers of X-linked retinal diseases on genetic testing and gene therapy: A global survey, Clinical Genetics (2024) https://doi.org/10.1111/cge.14442
Sam's parents struggled for years to obtain a diagnosis for his condition, but genetic research at CERA is finding answers.
Inherited retinal diseases are a broad group of genetic eye conditions that cause vision loss and sometimes, legal blindness. They can occur from birth through to late adulthood.
