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A human immunodeficiency syndrome caused by mutations in CARMIL2

Author

Listed:
  • T. Schober

    (Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität (LMU))

  • T. Magg

    (Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität (LMU))

  • M. Laschinger

    (Technische Universität München (TUM))

  • M. Rohlfs

    (Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität (LMU))

  • N. D. Linhares

    (Laboratory of Clinical Genomics, Federal University of Minas Gerais)

  • J. Puchalka

    (Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität (LMU))

  • T. Weisser

    (Technische Universität München (TUM))

  • K. Fehlner

    (Technische Universität München (TUM))

  • J. Mautner

    (Research Unit Gene Vectors, Helmholtz Zentrum München (HMGU)–German Research Center for Environmental Health
    Children’s Hospital, Technische Universität München (TUM)
    German Centre for Infection Research (DZIF))

  • C. Walz

    (Institute of Pathology, Ludwig-Maximilians-Universität (LMU))

  • K. Hussein

    (Institute of Pathology, Hannover Medical School (MHH))

  • G. Jaeger

    (Max von Pettenkofer-Institute, Ludwig-Maximilians-Universität (LMU))

  • B. Kammer

    (Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität (LMU))

  • I. Schmid

    (Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität (LMU))

  • M. Bahia

    (Federal University of Minas Gerais)

  • S. D. Pena

    (Laboratory of Clinical Genomics, Federal University of Minas Gerais)

  • U. Behrends

    (Research Unit Gene Vectors, Helmholtz Zentrum München (HMGU)–German Research Center for Environmental Health
    Children’s Hospital, Technische Universität München (TUM)
    German Centre for Infection Research (DZIF))

  • B. H. Belohradsky

    (Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität (LMU))

  • C. Klein

    (Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität (LMU)
    German Centre for Infection Research (DZIF))

  • F. Hauck

    (Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität (LMU)
    German Centre for Infection Research (DZIF))

Abstract

Human T-cell function is dependent on T-cell antigen receptor (TCR) and co-signalling as evidenced by immunodeficiencies affecting TCR-dependent signalling pathways. Here, we show four human patients with EBV+ disseminated smooth muscle tumours that carry two homozygous loss-of-function mutations in the CARMIL2 (RLTPR) gene encoding the capping protein regulator and myosin 1 linker 2. These patients lack regulatory T cells without evidence of organ-specific autoimmunity, and have defective CD28 co-signalling associated with impaired T-cell activation, differentiation and function, as well as perturbed cytoskeletal organization associated with T-cell polarity and migration disorders. Human CARMIL2-deficiency is therefore an autosomal recessive primary immunodeficiency disorder associated with defective CD28-mediated TCR co-signalling and impaired cytoskeletal dynamics.

Suggested Citation

  • T. Schober & T. Magg & M. Laschinger & M. Rohlfs & N. D. Linhares & J. Puchalka & T. Weisser & K. Fehlner & J. Mautner & C. Walz & K. Hussein & G. Jaeger & B. Kammer & I. Schmid & M. Bahia & S. D. Pen, 2017. "A human immunodeficiency syndrome caused by mutations in CARMIL2," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14209
    DOI: 10.1038/ncomms14209
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