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Journal of Clinical Immunology

, Volume 35, Issue 2, pp 112–118 | Cite as

Identification of a Novel Mutation in MAGT1 and Progressive Multifocal Leucoencephalopathy in a 58-Year-Old Man with XMEN Disease

  • Fatima Dhalla
  • Sarah Murray
  • Ross Sadler
  • Benjamin Chaigne-Delalande
  • Tomohiko Sadaoka
  • Elizabeth Soilleux
  • Gulbu Uzel
  • Joanne Miller
  • Graham Peter Collins
  • Christian Simon Ross Hatton
  • Malini Bhole
  • Berne Ferry
  • Helen M. Chapel
  • Jeffrey I. Cohen
  • Smita Y. Patel
Astute Clinician Report

Abstract

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 [1]. Functional studies have demonstrated roles for magnesium as a second messenger in T-cell receptor signalling [1], and for NKG2D expression and consequently NK- and CD8 T-cell cytotoxicity [2]. 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.

Keywords

XMEN Disease MAGT1 Epstein-Barr virus (EBV) progressive multifocal leucoencephalopathy (PML) 

Notes

Acknowledgments

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.

Supplementary material

10875_2014_116_MOESM1_ESM.docx (196 kb)
ESM 1 (DOCX 195 kb)

References

  1. 1.
    Li FY, Chaigne-Delalande B, Kanellopoulou C, Davis JC, Matthews HF, Douek DC, et al. Second messenger role for Mg2+ revealed by human T-cell immunodeficiency. Nature. 2011;475(7357):471–6.CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Chaigne-Delalande B, Li FY, O’Connor GM, Lukacs MJ, Jiang P, Zheng L, et al. Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D. Science. 2013;341(6142):186–91.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Li FY, Chaigne-Delalande B, Su H, Uzel G, Matthews H, Lenardo MJ. XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. Blood. 2014;123(14):1248–52.CrossRefGoogle Scholar
  4. 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. 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
  6. 6.
    Chikezie PU, Greenberg AL. Idiopathic CD4+ T lymphocytopenia presenting as progressive multifocal leukoencephalopathy: case report. Clin Infect Dis. 1997;24(3):526–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Haider S, Nafziger D, Gutierrez JA, Brar I, Mateo N, Fogle J. Progressive multifocal leukoencephalopathy and idiopathic CD4 + lymphocytopenia: a case report and review of reported cases. Clin Infect Dis. 2000;31(4):E20–2.CrossRefPubMedGoogle Scholar
  8. 8.
    Inhoff O, Doerries K, Doerries R, Scharf J, Groden C, Goerdt S, et al. Disseminated cutaneous Kaposi sarcoma and progressive multifocal leukoencephalopathy in a patient with idiopathic CD4+ T lymphocytopenia. Arch Dermatol. 2007;143(5):673–5.PubMedGoogle Scholar
  9. 9.
    Delgado-Alvarado M, Sedano MJ, González-Quintanilla V, de Lucas EM, Polo JM, Berciano J. Progressive multifocal leukoencephalopathy and idiopathic CD4 lymphocytopenia. J Neurol Sci. 2013;327(1–2):75–9.CrossRefPubMedGoogle Scholar
  10. 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. 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
  12. 12.
    Houff SA, Major EO, Katz DA, Kufta CV, Sever JL, Pittaluga S, et al. Involvement of JC virus-infected mononuclear cells from the bone marrow and spleen in the pathogenesis of progressive multifocal leukoencephalopathy. N Engl J Med. 1988;318(5):301–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Monaco MC, Atwood WJ, Gravell M, Tornatore CS, Major EO. JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: implications for viral latency. J Virol. 1996;70(10):7004–12.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Houff SA, Berger JR. The bone marrow, B cells, and JC virus. J Neurovirol. 2008;14(5):341–3.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Fatima Dhalla
    • 1
    • 2
  • Sarah Murray
    • 2
  • Ross Sadler
    • 3
  • Benjamin Chaigne-Delalande
    • 4
  • Tomohiko Sadaoka
    • 5
  • Elizabeth Soilleux
    • 6
  • Gulbu Uzel
    • 7
  • Joanne Miller
    • 1
    • 2
  • Graham Peter Collins
    • 8
  • Christian Simon Ross Hatton
    • 8
  • Malini Bhole
    • 9
  • Berne Ferry
    • 3
  • Helen M. Chapel
    • 1
    • 2
  • Jeffrey I. Cohen
    • 5
  • Smita Y. Patel
    • 1
    • 2
  1. 1.Nuffield Department of MedicineUniversity of OxfordOxfordUnited Kingdom
  2. 2.Department of Clinical ImmunologyJohn Radcliffe HospitalOxfordUnited Kingdom
  3. 3.Department of Clinical Laboratory ImmunologyChurchill HospitalOxfordEngland
  4. 4.Molecular Development Section, Lymphocyte Molecular Genetics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaMaryland
  5. 5.Laboratory of Infectious Diseases, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaMaryland
  6. 6.Nuffield Department of Clinical Laboratory SciencesUniversity of OxfordOxfordUnited Kingdom
  7. 7.Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaMaryland
  8. 8.Department of HematologyChurchill HospitalOxfordUnited Kingdom
  9. 9.Department of Clinical ImmunologyRussells Hall HospitalDudleyUnited Kingdom

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