A human immunodeficiency syndrome caused by mutations in CARMIL2


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.

DOI: 10.1038/ncomms14209

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@inproceedings{Schober2017AHI, title={A human immunodeficiency syndrome caused by mutations in CARMIL2}, author={Tilmann Schober and Thomas Magg and Melanie Laschinger and Meike Rohlfs and Nat{\'a}lia Duarte Linhares and J. Puchalka and Tillmann Wei\sser and Karin Fehlner and Josef Mautner and Christopher M Walz and Kais Hussein and Gundula Jaeger and Beatrix Kammer and Irene Schmid and Magda Bahia and S{\'e}rgio D. J. Pena and Uta Behrends and B. H. Belohradsky and Carmen Klein and Franziska Hauck}, booktitle={Nature communications}, year={2017} }