Genetics of progressive multifocal leukoencephalopathy: update on case reports with an inborn error of immunity and risk variants found in drug-linked cases.

ABSTRACT: A genetic predisposition to PML is now substantially supported by case reports of patients molecularly diagnosed with an inborn error of immunity (IEI) and progressive multifocal leukoencephalopathy (PML). Over the past 10 years, 4 IEI genes linked to PML has now grown to 26 as of 2025. Of these 26 genes believed to be causal of an IEI and PML, 24 (92%) are also linked with hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)-a severe hyper-inflammation syndrome associated with several IEI genes, most notably in 4 genes (PRF1, STX11, STXBP2, UNC13D) causing familial forms of the syndrome. Many HLH-linked genes are associated with life-threatening Epstein-Barr virus infections, which analogously suggests JC virus infection plus presence of

SUBMITTER: Eis PS 

PROVIDER: S-EPMC12320240 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature