Double Gene Mutation Adds on to The Risk of Multiple Sclerosis

Two new gene mutations are identified to cause multiple sclerosis (MS). This discovery adds on to the single gene mutation which causes MS

The "double gene" mutation was identified in a large Canadian family with five members diagnosed with MS - all of whom had the DNA abnormality.

‘Double mutations impair both immune function and phagocytosis, the process by which cells eliminate debris and pathogens. It also leads to the more typical "relapsing-remitting" form of MS, in which the symptoms come and go.’

Two other family members had the same mutation but didn't develop MS, indicating that some other genetic or environmental conditions are still necessary to trigger the disease process.

The discovery of this mutation should help erase doubts that at least some forms of MS are inherited. The prevailing view has been that a combination of many genetic variations causes a slight increase in susceptibility.

In this family, individuals with the double gene mutation have about a 7-in-10 chance of developing MS, compared to a 1-in-1,000 risk in the general population. These mutations, impair both immune function and phagocytosis, the process by which cells eliminate debris and pathogens.

"This is the first time that problems with phagocytosis have been linked to MS, and provides scientists with a better understanding the disease's origins and targets for developing new treatments," said lead author Carles Vilarino-Guell, an Assistant Professor of Medical Genetics who collaborated with colleagues at Australia's Florey Institute of Neuroscience and Mental Health.

The findings also could be used to screen people with a family history of the disease; an individual who was found to have this mutation could be a candidate for early diagnostic imaging long before symptoms appear, or could opt to reduce environmental risks by taking Vitamin D supplements or quitting smoking.

MS results from the body's immune system attacking myelin, the fatty material that insulates neurons and enables rapid transmission of electrical signals. When myelin is damaged, communication between the brain and other parts of the body is disrupted, leading to vision problems, muscle weakness, difficulty with balance and coordination, and cognitive impairments.

The double mutation, unlike the single mutation, leads to the more typical "relapsing-remitting" form of MS, in which the symptoms come and go. These differences in clinical symptoms suggests that different biological processes are responsible for each type of MS, which could explain why treatments for relapsing-remitting patients are ineffective for people with more debilitating, progressive form of the disease.

Source: Eurekalert