STIM1 Mutation Associated with a Syndrome of Immunodeficiency and Autoimmunity

doi:10.1056/NEJMoa0900082

Volume 360:1971-1980		May 7, 2009		Number 19

STIM1 Mutation Associated with a Syndrome of Immunodeficiency and Autoimmunity

Capucine Picard, M.D., Ph.D., Christie-Ann McCarl, B.S., Alexander Papolos, B.S., Sara Khalil, B.S., Kevin Lüthy, Claire Hivroz, Ph.D., Francoise LeDeist, M.D., Ph.D., Frédéric Rieux-Laucat, Ph.D., Gideon Rechavi, M.D., Anjana Rao, Ph.D., Alain Fischer, M.D., Ph.D., and Stefan Feske, M.D.

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SUMMARY

A mutation in ORAI1, the gene encoding the pore-forming subunitof the Ca²⁺-release–activated Ca²⁺ (CRAC) channel, abrogatesthe store-operated entry of Ca²⁺ into cells and impairs lymphocyteactivation. Stromal interaction molecule 1 (STIM1) in the endoplasmicreticulum activates ORAI1–CRAC channels. We report onthree siblings from one kindred with a clinical syndrome ofimmunodeficiency, hepatosplenomegaly, autoimmune hemolytic anemia,thrombocytopenia, muscular hypotonia, and defective enamel dentition.Two of these patients have a homozygous nonsense mutation inSTIM1 that abrogates expression of STIM1 and Ca²⁺ influx.

Source Information

From Assistance Publique–Hôpitaux de Paris, Hôpital Necker–Enfants Malades (C.P., F.L., A.F.), Laboratoire de Génétique Humaine des Maladies Infectieuses INSERM Unité 550, Necker Faculty (C.P.), Paris Descartes University (C.P., F.R.-L., A.F.), INSERM Unité 768 (C.H., F.L., F.R.-L., A.F.), and INSERM Unité 653 Curie Institut (C.H.) — all in Paris; New York University School of Medicine, New York (C.-A.M., A.P., S.K., K.L., S.F.); Centre Hospitalier Universitaire Sainte-Justine and University of Montreal, Montreal (F.L.); Chaim Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (G.R.); and Immune Disease Institute and Harvard Medical School, Boston (A.R.).

Drs. Fischer and Feske contributed equally to this article.

Address reprint requests to Dr. Feske at the Department of Pathology, New York University Langone Medical Center, 550 First Ave., New York, NY 10016, or at feskes01{at}nyumc.org.

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