X-linked inherited retinal dystrophy is a rare genetic eye condition that mostly affects males because it’s linked to the X chromosome. It causes problems with the retina, the part of the eye that detects light, leading to vision loss. The severity and age when it begins can vary, but it usually starts in childhood or young adulthood. This novel genetic discovery has been observed in 3 generations of the families involved in the study.
The team used genetic information from two different families where traditional genetic tests were unable to find the cause of their condition. They utilised stem cell technology methods to produce pluripotent stem cells which they pushed towards growing into Retinal Organoids (ROs) which are are three-dimensional structures that closely mimic the human retina. The ROs provide a working model of the affected area for the researchers to study in the laboratory.
The families in the study have remained genetically unresolved for decades but with new cutting-edge genetic techniques including Next Generation Sequencing, CUT&Tag and Hi-C , working with the ROs allowed our researchers to observe a new and very unusual genetic cause of disease.
The researchers didn’t find a change in a gene, but instead they found pieces of other chromosomes had jumped into the X-chromosome. These jumping parts are named insertions or structural variants. With the ROs, they could then look at these insertions and they discovered that they dysregulated a non-coding gene on the X chromosome. The dysregulation created by the structural variants interfered with how the gene is controlled in the retina.
The discovery will lead to further research in this area in addition to a better and earlier diagnosis rate for the condition.
Out BRC is committed to supporting studies for rare diseases as this work is crucial for advancing medical knowledge, improving patient care, and driving innovation in treatment development.
Research in rare diseases not only helps uncover the genetic and molecular mechanisms behind certain conditions but also provides valuable insights into more common diseases, as many rare disorders share biological pathways with widespread illnesses. Additionally, studying rare diseases encourages the development of novel therapies, such as gene and precision medicine, which can have broader applications. Increased awareness, funding, and research efforts are essential to ensure that individuals affected by rare diseases receive accurate diagnoses, effective treatments, and improved quality of life.