Genetic causes of diabetes in infants, pointing to a region of the genome that has long been overlooked in genetic research.
Most past studies have focused on “coding” genes, which contain instructions for making proteins. Researchers at the University of Exeter, working with international collaborators, have now identified a different source. They found that changes in two genes that produce functional RNA molecules can lead to diabetes. RNA has several roles in the body, including controlling gene activity and influencing how genetic information is “read” and interpreted.
With support from the National Institute for Health and Care Research NIHR Exeter Biomedical Research Centre and the Exeter NIHR Clinical Research Facility, the team used genome sequencing, a technique that reads the complete set of DNA instructions in a person.
This approach revealed that changes in two genes, RNU4ATAC and RNU6ATAC, caused autoimmune neonatal diabetes in 19 children. These children were identified through the University of Exeter’s global program, which offers free genetic testing to those suspected of having inherited forms of diabetes.
Understanding Neonatal Diabetes and Rare Diseases
Neonatal diabetes is a rare condition that appears within the first six months of life and is driven by genetic changes. Identifying its cause can lead to more targeted treatments and improved patient care. The findings also add to the broader understanding of rare diseases, which together affect about one in 17 people.
Study lead Associate Professor Elisa De Franco, of the University of Exeter Medical School, said, “For the first time, we found that DNA changes in non-protein coding genes cause neonatal diabetes. This shows the importance of non-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.”
How Genetic Changes Disrupt the Immune System
All 19 children in the study had an autoimmune form of diabetes, where the immune system attacks insulin-producing beta cells that control blood sugar. This same process occurs in type 1 diabetes.
