What is Wolfram Syndrome?
People with Wolfram Syndrome have mutations in the WFS1 gene. The WFS1 gene is active in cells throughout the body, with strong activity in the heart, brain, lungs, inner ear and pancreas. These mutations stop the body from producing Wolframin, an essential protein.
Within cells, Wolframin is located in a specialised structure called the endoplasmic reticulum. Among its many activities, the endoplasmic reticulum folds and modifies newly formed proteins so they have the correct 3-dimensional shape required to ensure normal cell function. Malfunctions in endoplasmic reticulum function cause accumulation of misfolded and unfolded proteins, a state called ER stress.
Cells cope with ER stress by activating an ER stress signalling network which helps proteins to fold properly. The result is that the ER stress resolves and the cells return to their normal function.
Wolframin plays an important role in controlling the regulatory feedback loop of the ER stress signalling network. In cells without Wolframin the endoplasmic reticulum remains in a permanent state of stress, causing the cells to die and organs such as the pancreas and brain to fail.
There is currently no approved treatment for Wolfram Syndrome and its diagnosis can be devastating for families. Because of the genetic nature of the condition, more than one child in a family can be diagnosed with Wolfram Syndrome.