New Gene Linked to Rare Form of Diabetes in Newborns

Researchers have discovered a specific gene associated with a rare type of diabetes that primarily affects newborns. Mutations within this gene can disrupt and eventually eliminate insulin-producing cells in the body.

This breakthrough sheds light on the pancreas’s beta cells—responsible for producing insulin, which regulates blood sugar levels—showing their reliance on the TMEM167A gene. Interestingly, this gene also plays a role in neuron function.

“Being able to derive insulin-producing cells from stem cells has allowed us to explore the dysfunction in beta cells found in patients with various forms of diabetes,” explains diabetologist Miriam Cnop from Free University of Brussels in Belgium. “This serves as a remarkable model for both understanding disease mechanics and testing potential therapies.”

The international research team analyzed the genetic information of six infants diagnosed with neonatal diabetes, some also exhibiting microcephaly. Notably, five of these infants suffered from epilepsy as well.

This cluster of conditions in infants is referred to as MEDS (microcephaly, epilepsy, and diabetes syndrome), and it is exceptionally rare, with only 11 cases documented to date.

Before this research, two other genes had been linked to MEDS: IER3IP1 and YIPF5. For an infant to be born with MEDS, they need to inherit two copies of the mutated gene—one from each parent.

Gene sequencing revealed that this same inheritance pattern also applies to babies with the insulin-blocking variant of the TMEM167A gene, marking it as the third known genetic cause of MEDS.

The TMEM167A gene is active in both the pancreas and brain across various species, including humans and mice. This activity could help explain the organ-related issues these infants face.

In an effort to understand how the variant of the TMEM167A gene leads to diabetes, researchers removed the gene from human pluripotent stem cells and replaced it with the variant derived from a MEDS patient. These stem cells were then stimulated to develop into beta cells.

Although the gene variant did not hinder the development of these cells, they were significantly non-functional. When exposed to glucose, the beta cells failed to release insulin as intended.

Furthermore, these cells struggled with disruptions to their endoplasmic reticulum, a critical cellular structure, ultimately leading to beta cell death.

“Identifying the DNA alterations responsible for diabetes in infants gives us a valuable avenue for pinpointing genes crucial for insulin production and secretion,” states Elisa de Franco, a molecular geneticist from the University of Exeter.

“Discovering these particular DNA changes linked to this rare type of diabetes in six children contributed to clarifying the function of the lesser-known gene, TMEM167A, and how it is integral to insulin secretion.”

This research findings were published in The Journal of Clinical Investigation.