An international team of researchers has identified a previously unknown type of diabetes in newborns caused by mutations in the TMEM167A gene. This rare condition leads to both high blood sugar and neurological issues like epilepsy and microcephaly. The findings, published in a leading medical journal, could enhance understanding of insulin production in broader diabetes research.
Researchers from the University of Exeter Medical School and Université Libre de Bruxelles, along with global partners, used advanced DNA sequencing and stem cell models to uncover this hidden diabetes variant. The study focused on six infants who developed diabetes within their first six months of life, a period when over 85 percent of such cases stem from genetic changes. These children also exhibited neurological symptoms, including epilepsy and microcephaly, all linked to recessive mutations in the TMEM167A gene.
To investigate the gene's role, scientists at ULB converted stem cells into pancreatic beta cells—the insulin producers—and employed CRISPR gene-editing to mimic the mutations. The experiments revealed that damaged TMEM167A impairs cell function under stress, triggering responses that cause cell death and disrupt insulin secretion.
Dr. Elisa de Franco from the University of Exeter highlighted the breakthrough: "Finding the DNA changes that cause diabetes in babies gives us a unique way to find the genes that play key roles in making and secreting insulin. In this collaborative study, the finding of specific DNA changes causing this rare type of diabetes in 6 children, led us to clarifying the function of a little-known gene, TMEM167A, showing how it plays a key role in insulin secretion."
Professor Miriam Cnop added: "The ability to generate insulin-producing cells from stem cells has enabled us to study what is dysfunctional in the beta cells of patients with rare forms as well as other types of diabetes. This is an extraordinary model for studying disease mechanisms and testing treatments."
The TMEM167A gene proves essential for beta cells and neurons but less so for other tissues, offering insights into insulin biology. While rare, the discovery may guide research into common diabetes, which impacts nearly 589 million people globally. The work, funded by organizations including Diabetes UK and the Novo Nordisk Foundation, appears in The Journal of Clinical Investigation under the title 'Recessive TMEM167A variants cause neonatal diabetes, microcephaly and epilepsy syndrome.'
