New research has looked into MEDS syndrome, an incredibly rare disease that affects babies in the first six months of life.
An international team of scientists has identified a single gene responsible for a rare and devastating form of diabetes found in newborns. The gene, known as TMEM167A, has been shown to play a crucial role in the survival and function of insulin-producing cells in the pancreas. Mutations in this gene can destroy these cells, leading to a condition that also affects brain development.
The discovery provides clues about a rare disease called MEDS syndrome — short for microcephaly, epilepsy and diabetes syndrome — that affects babies in first six months of life. Only 11 cases have been recorded worldwide. In the new study, researchers analyzed the genomes of six babies with MEDS. All had been diagnosed with neonatal diabetes and microcephaly, and five also suffered from epilepsy, says the .
Previously, scientists had associated two other genes, IER3IP1 and YIPF5, with the syndrome. The new findings, in The Journal of Clinical Investigation by an international consortium of investigators, confirm TMEM167A as the third genetic cause of MEDS. Like the other forms, the condition arises when a baby inherits two defective copies of the same gene, one from each parent.
The TMEM167A gene is active in both the pancreas and brain and in both humans and mice, which may explain why MEDS patients experience dysfunction in both organs. To understand its role, the team used human stem cells to recreate the disease process in the laboratory. When they replaced the normal TMEM167A gene with the variant found in a patient with MEDS, the cells successfully developed into pancreatic beta cells, but did not work properly.
These defective beta cells did not release insulin in response to glucoselike healthy cells, and also presented severe stress in their endoplasmic reticulum, which led to cell death.
“Discovering the changes in DNA that cause diabetes in babies gives us a unique way of finding the genes that play important roles in insulin production and secretion,” says molecular geneticist Elisa de Franco from the University of Exeter.
