Researchers Find Gene Mutation in Multiple Sclerosis That Runs in Families

A variation in the NLRP1 gene is associated with multiple sclerosis that runs in families, Slovenian researchers report.

Their study, “Identification of rare genetic variation of NLRP1 gene in familial multiple sclerosis,” was published in the journal Scientific Reports. The research was led by Dr. Borut Peterlin of Ljubljana University Medical Center’s Clinical Institute of Medical Genetics.

Scientists believe MS arises from a combination of a person’s genetic background and the environment. Although previous studies have suggested that genes are behind MS that runs in families, researchers had yet to confirm that hypothesis.

The Slovenian team wanted to identify any genes that were at play in both the MS and malignant melanoma that two siblings had. Although disease surveys indicate the two conditions can occur together, scientists had been unable to identify a shared cause for the two conditions.

Interestingly, research has shown a link between a person’s susceptibility to MM and a mutation of the NLRP1 gene. And recent studies have indicated that NLRP1 plays a role in the development of MM.

The Slovenian team decided to evaluate the association between an NLRP1 mutation and multiple sclerosis in two groups. One consisted of 38 people with MS whose disease ran in the family. The other was 44 people with MS whose disease did not run in their family.

Researchers used genomic, molecular biology and immunology measurements to decide whether there was a link between the mutation and MS.

They found a connection between the mutation and MS that runs in families. The mutation affects the function of the protein the gene generates — a protein known to be involved in inflammatory processes.

Researchers also found other NLRP1 mutations in patients with and without a family history of MS that they believe could be involved in the development of the disease.

In addition, the team found evidence of a connection between MS associated with NLRP1 mutations and the development of MM. That evidence involved immune responses to the two conditions.

Stimulating the production of immune-system components known as peripheral blood mononuclear cells, or PBMCs, triggered immune responses in MS patients with NLRP1 mutations. The responses included increased production of the pro-inflammatory cytokine IL-1β. Higher levels of that protein have been found in MM tissue.

PBMCs include such immune cells as lymphocytes, monocytes, and macrophages.

“IL-1β has been implicated in a variety of inflammatory and neurodegenerative processes occurring in MS,” the researchers wrote.

Overall, the findings demonstrated an association between MS running in families and MM, they said. And the genetic link between the two may be the NLRP1 gene mutation, they added.

The team said scientists might be able to develop a treatment for MS by finding a way to lower the increased production of IL-1β that NLRP1 mutations trigger.