An international research team has uncovered a novel form of diabetes that arises in infants under six months of age. In most reported cases — more than 85 percent — the condition appears to stem from a mutation in their genetic code.
The investigators, from the University of Exeter in the U.K. and Université Libre de Bruxelles (ULB), pinpointed alterations in a gene called TMEM167A, which appears to underlie this rare neonatal diabetes. In six children exhibiting additional neurological symptoms — such as epilepsy and a smaller head size (microcephaly) — mutations in TMEM167A were detected.
“Uncovering the exact DNA changes responsible for diabetes in these infants offers a unique window into the genes that are critical for insulin production and secretion,” explained Dr. Elisa de Franco of the University of Exeter. Using cutting-edge DNA sequencing, she and her collaborators traced the cause of this rare form of early-onset diabetes to defects in the TMEM167A gene.
To explore how the mutation works, the team used stem cells differentiated into pancreatic beta cells, along with CRISPR gene editing tools. They discovered that when TMEM167A is defective, insulin-secreting beta cells lose functionality, triggering stress responses that lead to cell death.
Professor Miriam Cnop of ULB added: “The capacity to generate insulin-producing cells from stem cells allows us to observe the precise defects in beta cells associated with rare diabetes variants — and potentially other forms of the disease. It’s an extraordinary model for investigating disease mechanisms and developing therapies.”
Their findings, published in the Journal of Clinical Investigation, reveal that TMEM167A is critical not only for beta-cell function but also for neuronal health, though it seems less essential in other cell types. This discovery offers fresh insight into how insulin production is regulated and may guide future research into more common forms of diabetes — a condition that currently affects nearly 589 million people worldwide.