Researchers Discover Rare New Type of Diabetes Affecting Newborns Worldwide

A little-known gene turns out to be vital for insulin production in the earliest stages of life.

Recent advances in DNA sequencing, combined with new stem cell research approaches, have allowed an international group of scientists to identify a previously unrecognized form of diabetes that appears in infancy.

Researchers at the University of Exeter Medical School, working alongside colleagues at Université Libre de Bruxelles (ULB) in Belgium and other institutions, determined that changes in the TMEM167A gene are responsible for this rare type of neonatal diabetes.

Diabetes can emerge in some babies within the first six months of life, and in more than 85 percent of these cases, the cause lies in inherited genetic mutations. In a study led by the University of Exeter, scientists examined six children who also had neurological conditions such as epilepsy and microcephaly and found that all shared alterations in a single gene, TMEM167A.

Stem cell and gene-editing insights into TMEM167A

To clarify how this gene functions, Professor Miriam Cnop’s team at ULB used stem cells that were guided to become pancreatic beta cells and applied gene editing techniques (CRISPR). Their experiments showed that when TMEM167A is disrupted, insulin-producing cells lose their ability to function properly. As a result, these cells trigger stress responses that ultimately lead to their death.

Dr. Elisa de Franco, at the University of Exeter, said: “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 Cnop said: “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.”

Broader implications for diabetes biology

This discovery shows that the TMEM167A gene is essential for the proper functioning of insulin-producing beta cells, but also for neurons, whereas it seems dispensable for other cell types.

These results contribute to a better understanding of the crucial steps involved in insulin production and could shed light on research into other forms of diabetes, a disease which today affects almost 589 million people worldwide.

Reference: “Recessive TMEM167A variants cause neonatal diabetes, microcephaly, and epilepsy syndrome” by Enrico Virgilio, Sylvia Tielens, Georgia Bonfield, Fang-Shin Nian, Toshiaki Sawatani, Chiara Vinci, Molly Govier, Hossam Montaser, Romane Lartigue, Anoop Arunagiri, Alexandrine Liboz, Flavia Natividade Da Silva, Maria Lytrivi, Theodora Papadopoulou, Matthew N. Wakeling, James Russ-Silsby, Pamela Bowman, Matthew B. Johnson, Thomas W. Laver, Anthony Piron, Xiaoyan Yi, Federica Fantuzzi, Sirine Hendrickx, Mariana Igoillo-Esteve, Bruno J. Santacreu, Jananie Suntharesan, Radha Ghildiyal, Darshan Hegde, Nikhil Shah, Sezer Acar, Beyhan Özkaya Dönmez, Behzat Özkan, Fauzia Mohsin, Iman M. Talaat, Mohamed Tarek Abbas, Omar Tarek Abbas, Hamed Ali Alghamdi, Nurgun Kandemir, Sarah E. Flanagan, Raphael Scharfmann, Peter Arvan, Matthieu Raoux, Laurent Nguyen, Andrew T. Hattersley, Miriam Cnop and Elisa De Franco, 9 September 2025, The Journal of Clinical Investigation.
DOI: 10.1172/JCI195756

The study was supported by Diabetes UK, the European Foundation for the Study of Diabetes and Novo Nordisk foundation, the ULB Foundation, the FNRS, the FRFS-WELBIO, the Research Foundation Flanders (FWO) and the Excellence of Science (EOS) program. Dr. De Franco is supported by the NIHR Exeter Biomedical Research Centre.

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