Scientists at the University of Exeter and their international collaborators announced on Apr. 9 that they have identified new genetic causes for diabetes in infants, focusing on a part of the genome that has not been widely studied before.
This research is significant because it shifts attention from protein-coding genes to non-coding regions of DNA, which play important roles in gene regulation. The findings could help improve diagnosis and treatment options for rare forms of diabetes and other rare diseases.
The team discovered that changes in two genes, RNU4ATAC and RNU6ATAC, which produce functional RNA molecules rather than proteins, were responsible for autoimmune neonatal diabetes in 19 children. Neonatal diabetes is a rare condition that appears within the first six months of life due to genetic mutations. The children were identified through free global genetic testing provided by the University of Exeter.
Associate Professor Elisa De Franco said, "For the first time, we found that DNA changes in non-protein coding genes cause neonatal diabetes. This shows the importance of non-protein coding genes and their potential to cause disease in humans. With up to half of individuals with rare diseases currently living without a diagnosis, exploring the non-coding DNA can provide answers for families with rare conditions."
Researchers used advanced laboratory and computational techniques to analyze samples from affected children. They found these gene mutations disrupted about 800 other genes linked to immune system function. Dr Matthew Johnson said, "This finding is important as highlights that one or more of these 800 genes has a central role in the development of autoimmune diabetes, and could uncover new biology and potential drug targets for more common type 1 diabetes." He added: "Whilst the condition caused by these genetic changes is rare, it provides us with unique opportunities to study the pathways that lead to autoimmune forms of diabetes in humans, giving us a window into the ways type 1 diabetes can develop".
The study was published under the title 'Bi-allelic variants in the non-protein-coding minor spliceosome components RNU6ATAC and RNU4ATAC cause syndromic monogenic autoimmune diabetes' in The American Journal of Human Genetics. It will also be presented at an upcoming conference hosted by the European Society of Human Genetics.
