title: Progressive multifocal leukoencephalopathy in an immunocompetent patient.
abstract: Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain, is typically diagnosed in immunocompromised persons. Here, we describe the diagnostic challenge of PML in an apparently immunocompetent patient. Thorough analyses, including cytokine release assays and whole exome sequencing, revealed a deficit in the antiviral interferon gamma production capacity of this patient and compound heterozygous mutations in BCL-2-associated athanogene 3. Interestingly, both factors are associated with reduced expression of John Cunningham virus T-antigen, a protein that plays a key role in viral replication in infected cells. After validation in other patients, our findings may contribute to novel insights into the etiology and possibly treatment of PML.
authors.affiliation: Department of Neurology Radboud University Medical Center Nijmegen The Netherlands.
authors.forename: Nicolien M
authors.initials: NM
authors.lastname: van der Kolk
authors.affiliation: Department of Genetics Radboud University Medical Center Nijmegen The Netherlands.
authors.forename: Peer
authors.initials: P
authors.lastname: Arts
authors.affiliation: Department of Neurology Radboud University Medical Center Nijmegen The Netherlands.
authors.forename: Ingeborg W M
authors.initials: IW
authors.lastname: van Uden
authors.affiliation: Department of Genetics Radboud University Medical Center Nijmegen The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hoischen
authors.affiliation: Department of Internal Medicine Radboud University Medical Center Nijmegen The Netherlands.
authors.forename: Frank L
authors.initials: FL
authors.lastname: van de Veerdonk
authors.affiliation: Department of Internal Medicine Radboud University Medical Center Nijmegen The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Neurology Radboud University Medical Center Nijmegen The Netherlands; Department of Neurology VU University Medical Center Amsterdam The Netherlands.
authors.forename: Brigit A
authors.initials: BA
authors.lastname: de Jong