Identification of a Novel Mutation in MAGT1 and Progressive Multifocal Leucoencephalopathy in a 58-Year-Old Man with XMEN Disease
- 720 Downloads
XMEN disease (X-linked immunodeficiency with Magnesium defect, Epstein-Barr virus infection and Neoplasia) is a novel primary immune deficiency caused by mutations in MAGT1 and characterised by chronic infection with Epstein-Barr virus (EBV), EBV-driven lymphoma, CD4 T-cell lymphopenia, and dysgammaglobulinemia . Functional studies have demonstrated roles for magnesium as a second messenger in T-cell receptor signalling , and for NKG2D expression and consequently NK- and CD8 T-cell cytotoxicity . 7 patients have been described in the literature; the oldest died at 45 years and was diagnosed posthumously [1, 2, 3]. We present the case of a 58-year-old Caucasian gentleman with a novel mutation in MAGT1 with the aim of adding to the phenotype of this newly described disease by detailing his clinical course over more than 20 years.
KeywordsXMEN Disease MAGT1 Epstein-Barr virus (EBV) progressive multifocal leucoencephalopathy (PML)
This work was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases. We thank Tammy Krogmann for preparing RNA and cDNA from the nephew.
- 4.Sadler R, Bateman EA, Heath V, Patel SY, Schwingshackl PP, Cullinane AC, et al. Establishment of a healthy human range for the whole blood ’OX40′ assay for the detection of antigen-specific CD4+ T cells by flow cytometry. Cytometry B Clin Cytom. 2014.Google Scholar
- 5.Misbah SA, Spickett GP, Zeman A, Esiri MM, Wallington TB, Kurtz JB, et al. Progressive multifocal leucoencephalopathy, sclerosing cholangitis, bronchiectasis and disseminated warts in a patient with primary combined immune deficiency. J Clin Pathol. 1992;45(7):624–7.CrossRefPubMedCentralPubMedGoogle Scholar
- 10.Carson KR, Focosi D, Major EO, Petrini M, Richey EA, West DP, et al. Monoclonal antibody-associated progressive multifocal leucoencephalopathy in patients treated with rituximab, natalizumab, and efalizumab: a review from the research on adverse drug events and reports (RADAR) project. Lancet Oncol. 2009;10(8):816–24.CrossRefPubMedGoogle Scholar
- 11.Ferenczy MW, Marshall LJ, Nelson CD, Atwood WJ, Nath A, Khalili K, et al. Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev. 2012;25(3):471–506.CrossRefPubMedCentralPubMedGoogle Scholar