Scientists are zeroing in on mutations in a few genes that appear to be major risk factors for developing multiple sclerosis (MS). The results of their research suggest there are common biological pathways that cause the disease.
The study, “Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease,” was published in the journal PLOS Genetics.
Only about 13% of people diagnosed with MS have a close biological relative also diagnosed with the disease. In these cases, the likelihood of developing MS often is influenced significantly by one, or only a few, mutations that run in the family.
In the study, a team led by researchers at The University of British Columbia, Canada, analyzed 34 families of European descent with a family history of MS. The team looked for mutations in 132 MS patients, as well as non-affected relatives, using whole-exome sequencing — a technology that sequences only the part of the genome that actually generates proteins (called the exome).
By determining which genetic mutations were more likely to be present in individuals with MS, but not in unaffected individuals, researchers were able to identify 12 mutations tied to a greater likelihood of developing MS.
According to the team, the affected 12 genes — namely PLAU, MASP1, C2, NLRP12, UBR2, CTNNA3, NFATC2, RNF213, NCOA3, KCNG4, SLC24A6, and SLC8B1 — may provide clues about which biological processes are affected and may lead to MS.
“These genes are like a lighthouse illuminating where the root cause of MS is,” Carles Vilariño-Güell, PhD, co-author of the study, said in a press release.
The 12 genes identified in the analysis are involved in only a few biological pathways, most of which have known immunological and inflammatory roles. This suggests the disruption of these pathways may be the cause of MS, and might provide an avenue for exploring treatment strategies.
“We have treatments that address the symptoms of MS, but not the causes. People with MS take drugs that reduce the attacks, but the disease still progresses,” Vilariño-Güell said. “Now, with knowledge of these mutations, which suggest a common biological process that leads to increased inflammation in MS families, we can try to address the root causes.”
The researchers now plan to develop cell and animal models of these mutations in order to better understand how they might play a role in developing MS.