• Fahad Alsohime, Marta Martin-Fernandez, Mohamad-Hani Temsah, Majed Alabdulhafid, Tom Le Voyer, Malak Alghamdi, Xueer Qiu, Najla Alotaibi, Areej Alkahtani, Sofija Buta, Emmanuelle Jouanguy, Ayman Al-Eyadhy, Conor Gruber, Gamal M Hasan, Fahad A Bashiri, Rabih Halwani, Hamdy H Hassan, Saleh Al-Muhsen, Nouf Alkhamis, Zobaida Alsum, Jean-Laurent Casanova, Jacinta Bustamante, Dusan Bogunovic, and Abdullah A Alangari.
• From the Department of Pediatrics (F.A., M.-H.T., M. Alabdulhafid, M. Alghamdi, N. Alotaibi, A.A., A.A.-E., G.M.H., F.A.B., S.A.-M., N. Alkhamis, Z.A., A.A.A.) and the Immunology Research Laboratory, Department of Pediatrics (R.H., S.A.-M.), College of Medicine, King Saud University, the Department of Pediatrics, College of Medicine, Imam Mohammed bin Saud University (A.A.), and the Department of Radiology and Medical Imaging, King Saud University Medical City (H.H.H.) - all in Riyadh, Saudi Arabia; the Departments of Microbiology and Pediatrics and the Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai (M.M.-F., X.Q., S.B., C.G., D.B.), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, the Rockefeller University (E.J., J.-L.C., J.B.), and Howard Hughes Medical Institute (J.-L.C.) - all in New York; Paris Descartes University, Imagine Institute, and the Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM Unité 1163 (T.L.V., E.J., J.-L.C., J.B.), and the Pediatric Hematology and Immunology Unit (J.-L.C.) and the Center for the Study of Primary Immunodeficiencies (J.B.), Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children - all in Paris; the Department of Pediatrics, Assiut Faculty of Medicine, Assiut University, Assiut, Egypt (G.M.H.); and Sharjah Institute for Medical Research, Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates (R.H.).
• N. Engl. J. Med. 2020 Jan 16; 382 (3): 256265256-265.

AbstractDeficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure. Exome sequencing identified a homozygous mutation at an essential splice site on USP18. The encoded protein was expressed but devoid of negative regulatory ability. Treatment with ruxolitinib was followed by a prompt and sustained recovery. (Funded by King Saud University and others.).Copyright © 2020 Massachusetts Medical Society.

42 keywords...

hide…