Four Genetic Markers Connected to Progressive Multifocal Leukoencephalopathy

Scientists whose research has been published in Frontiersin Neurology have identified 4 specific genes associated with progressive multifocal leukoencephalopathy (PML). The 4 genes are C8B, LY9 (also known as SLAMF3), FCN2, and STXBP2, and it is hoped that eventually genetic screening may be helpful in identifying those at risk for PML---a rare but potentially life-threatening infection that can be triggered in those taking immune-modifying medications, including some drugs commonly prescribed for managing multiple sclerosis (MS). PML is caused by the polyomavirus, JC virus (JCV). In 2021, there were more than 500 cases of PML reported in the FDA’s adverse event reporting system. 

Analyzing data available through the Genome Aggregation Database (gnomAD), researchers validated that four genetic variants were more common in those who developed PML while taking immunosuppressant drugs than in the general population. Researchers then confirmed the association by comparing the genetic profiles of 2 groups: 1) those infected with JCV who developed PML while taking immune-modifying agents, and 2) those infected with JCV who did not develop PML while taking immune-modifying agents. They found that individuals who were carriers of any of the four genetic variants were 9 times more likely to develop PML than those who were not carriers. 

"It's critical to be able to identify genetic mutations that greatly increase a person's risk of this devastating infection," commented Dr. Lawrence Steinman, professor of neurology and neurological sciences, pediatrics, and genetics at Stanford University.