An international team of scientists has identified a previously unknown genetic form of diabetes that affects babies, offering new insights into how insulin-producing cells can fail early in life. Using advanced DNA sequencing techniques and stem cell research models, the discovery sheds light on the biological mechanisms behind this rare condition.
The research was led by the University of Exeter Medical School in collaboration with the Université Libre de Bruxelles (ULB) in Belgium, alongside other international partners. The team found that mutations in a gene known as TMEM167A are responsible for this newly identified form of neonatal diabetes.
Neonatal diabetes typically develops within the first six months of life, and in more than 85 percent of cases, it is caused by inherited genetic changes. In the study, researchers examined six children who presented not only with early-onset diabetes but also with neurological conditions, including epilepsy and microcephaly.
Genetic analysis revealed that all six children shared mutations in the same gene, TMEM167A, indicating a single genetic cause underlying both the metabolic disorder and the associated neurological symptoms.
A team led by Professor Miriam Cnop at ULB used stem cells that were transformed into pancreatic beta cells—the cells responsible for producing insulin. Using CRISPR gene-editing technology, the researchers altered the TMEM167A gene to observe its effects on cell function.
The experiments showed that damage to TMEM167A disrupts the normal function of insulin-producing cells. As cellular stress accumulates, internal stress responses are triggered, eventually leading to the death of these vital cells and the onset of diabetes.
Explaining the significance of the findings, Dr. Elisa de Franco of the University of Exeter said the discovery provides a powerful pathway for understanding how insulin is made and secreted in the body. She noted that identifying the DNA changes responsible for this rare form of diabetes has helped clarify the role of a previously little-known gene and its critical function in insulin secretion.
Professor Cnop highlighted the broader implications of the research, emphasizing that the ability to generate insulin-producing cells from stem cells allows scientists to study what goes wrong in beta cells in rare and more common forms of diabetes. She added that the TMEM167A gene is essential not only for pancreatic beta cells but also for neurons, while appearing to play a lesser role in many other cell types.
Researchers say the findings could also inform future studies into more common forms of diabetes, a disease that currently affects nearly 589 million people worldwide, potentially opening new avenues for understanding, prevention, and treatment.