Rare Neonatal Diabetes Syndrome Linked to TMEM167A Gene Mutations in New Genetic Discovery

A genetic mutation identified in six infants could rewrite understanding of diabetes' origins—and explain why some children develop both diabetes and neurological disorders shortly after birth.

Researchers have linked TMEM167A gene mutations to a rare neonatal diabetes syndrome affecting infants with diabetes, microcephaly, and epilepsy.

By analyzing DNA changes in these patients, Dr. Elisa de Franco of the University of Exeter noted that such discoveries provide a unique pathway to identify genes critical for insulin production and secretion.

"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," she explained.

Professor Miriam Cnop of ULB added that stem cell modeling has enabled researchers to study dysfunctional beta cells in rare and common diabetes forms.

"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," she stated.

Using CRISPR-edited stem cells, the team revealed that TMEM167A dysfunction triggers cell death in insulin-producing beta cells and neurons. This dual metabolic and neurological impact distinguishes the condition from other diabetes syndromes.

The study estimates that TMEM167A mutations account for approximately 15% of neonatal diabetes cases, which occur in 1 in 100,000 births. With 589 million people globally affected by diabetes, these findings could inform broader research into disease mechanisms.

The research, published in The Journal of Clinical Investigation (DOI: 10.1172/JCI195756), was funded by Diabetes UK, the Novo Nordisk Foundation, and other institutions.

The team emphasizes the need for further studies to validate these findings and explore therapeutic interventions.