Advanced DNA sequencing technologies and a new model of stem cell research has enabled an international team to discover a new type of diabetes in babies.
The University of Exeter Medical School worked with Université Libre de Bruxelles (ULB) in Belgium and other partners to establish that mutations in the TMEM167A gene are responsible for a rare form of neonatal diabetes.
Some babies develop diabetes before the age of six months. In over 85 per cent of cases this is due genetic mutation in their DNA. Research led by the University of Exeter found that in six children with additional neurological disorders such as epilepsy and microcephaly identified alterations in a single gene: TMEM167A.
To understand its role, ULB researcher Professor Miriam Cnop's team used stem cells differentiated into pancreatic beta cells and gene-editing techniques (CRISPR). They found that when the TMEM167A gene is altered, insulin-producing cells can no longer fulfill their role. They then activate stress mechanisms that 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."
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.
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.
