Genetic mutation discovered in two brothers

Genetic mutation discovered in two brothers. The researchers are convinced that this discovery will help progress in the search for new treatments for type 1 diabetes. Specifically, British researchers from the University of Exeter have made a startling discovery, namely a unique genetic mutation identified in two brothers, who did not it has also been discovered in humans.

Genetic mutation discovered in two brothers

The mutation is in the gene for a protein called PD-L1 (programmed cell death ligand 1) that acts as a kind of “brake” to keep the body’s immune responses under control. The new study explains how the protein may be responsible for the autoimmune form of diabetes that children developed at a very young age.

“We’ve searched the globe, looking at all the large-scale data sets we know of, and we haven’t been able to find another family. These siblings therefore provide us with a unique and incredibly important opportunity to investigate what happens when this gene is switched off in humans,” explained molecular geneticist Matthew Johnson, from the University of Exeter.

Genetic mutation discovered in two brothers. Photo source: Pixabay

Type 1 diabetes (autoimmune diabetes) is a devastating disease

Type 1 diabetes is also known as autoimmune diabetes because of the way the body’s built-in immune system attacks the pancreatic beta cells, stopping normal insulin production.

People with this condition must inject insulin regularly to manage their blood sugar levels. The two brothers, aged 10 and 11 at the time of the study, developed diabetes in the first weeks of life.

A closer look at the immune cells present in the two children confirmed that their unique genetic mutation prevented the PD-L1 protein from working properly.

The PD-L1 protein has a key role in preventing the onset of diabetes

Since PD-L1 and its receptor PD-1 combine as a sort of safety mechanism to keep the immune system in check, and cancer treatments that block PD-L1 functions can also lead to diabetes, it appears that PD-L1 protein has a key role in preventing type 1 diabetes.

However, in a surprising twist, it turned out that the immune systems of the two young brothers were functioning quite normally, even without the regulation of the immune system that PD-L1 and PD-1 normally provide.

“We believe that PD-L2, another ligand of PD-1, although less studied than PD-L1, could serve as a backup system when PD-L1 is not available,” says researcher Masato Ogishi of the University Rockefeller of New York.

Genetic mutation discovered in two brothers. Photo source: Pixabay

Genetic mutation that could help understand the development of autoimmune forms of diabetes

A key conclusion the researchers reached is that the PD-L1 protein is essential for preventing type 1 diabetes, but not as important for maintaining many other functions of the immune system.

The clues provided by the discovery of this genetic mutation, plus the link between cancer treatment and diabetes, could help unlock new ways to approach the onset of type 1 diabetes – if researchers can learn how PD-L1 prevents it and how PD-L2 act as a backup solution.

“Now we need to find out what is the communication between the different types of cells, which is essential for the prevention of autoimmune diabetes. This discovery increases our knowledge of how autoimmune forms of diabetes such as type 1 diabetes develop and points to a potential new target for treatments that could prevent diabetes in the future,” explained immunologist Timothy Tree from King’s College London, according to news-medical.