Genetic cause of multiple sclerosis

Scientists at the University of British Columbia and Vancouver Coastal Health have proven that multiple sclerosis can be caused by a single genetic mutation—a rare alteration in DNA that makes it very likely a person will develop the more devastating form of the neurological disease.

The mutation was found in two Canadian families that had several members diagnosed with a rapidly progressive type of MS. The discovery of this mutation should erase doubts that at least some forms of MS are inherited. The prevailing view has been that a combination of many genetic variations cause a slight increase in susceptibility. In the two families described in this study, two-thirds of the people with the mutation developed the disease.

Canada has one of the highest rates of MS in the world. An estimated 100 000 Canadians are living with MS, and the disease is most often diagnosed in young adults, aged 15 to 40. Although only one in 1000 MS patients appears to have this mutation, its discovery helps reveal the biological pathway that leads to the rapidly progressive form of the disease, accounting for about 15% of people with MS. The discovery could also provide insight into the more common, relapsing-remitting form of MS, because that disease gradually becomes progressive in most cases.

Co-author Dr Anthony Traboulsee, the MS Society of Canada Research Chair at UBC and director of Vancouver Coastal Health’s MS and Neuromyelitis Optica Clinic, notes that if a person has this gene, chances are they will develop MS and rapidly deteriorate. Screening for the mutation in high-risk individuals could enable earlier diagnosis and treatment before symptoms appear.

The findings could also help in the search for therapies that act on the gene itself or counteract the mutation’s disease-causing effects.

Senior author Dr Carles Vilarino-Guell, assistant professor of medical genetics, and member of the Djavad Mowafaghian Centre for Brain Health, suggests that the mutation puts people at the edge of a cliff, but something still has to give them the push to set the disease process in motion.

The families with this mutation had donated to a Canada-wide collection of blood samples from people with MS, begun in 1993 by co-author Dr A. Dessa Sadovnick, a UBC professor of medical genetics and neurology. The 20-year project has samples from 4400 people with MS, plus 8600 blood relatives.

The study, “Nuclear receptor NR1H3 in familial multiple sclerosis,” is published in the journal Neuron and is available online at http://dx.doi.org/10.1016/j.neuron.2016.04.039.