TY - JOUR
T1 - JAK inhibitor therapy in a child with inherited usp18 deficiency
AU - Alsohime, Fahad
AU - Martin-Fernandez, Marta
AU - Temsah, Mohamad Hani
AU - Alabdulhafid, Majed
AU - Le Voyer, Tom
AU - Alghamdi, Malak
AU - Qiu, Xueer
AU - Alotaibi, Najla
AU - Alkahtani, Areej
AU - Buta, Sofija
AU - Jouanguy, Emmanuelle
AU - Al-Eyadhy, Ayman
AU - Gruber, Conor
AU - Hasan, Gamal M.
AU - Bashiri, Fahad A.
AU - Halwani, Rabih
AU - Hassan, Hamdy H.
AU - Al-Muhsen, Saleh
AU - Alkhamis, Nouf
AU - Alsum, Zobaida
AU - Casanova, Jean Laurent
AU - Bustamante, Jacinta
AU - Bogunovic, Dusan
AU - Alangari, Abdullah A.
N1 - Publisher Copyright:
© 2020 Massachusetts Medical Society.
PY - 2020/1/16
Y1 - 2020/1/16
N2 - Deficiency 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.
AB - Deficiency 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.
UR - https://www.scopus.com/pages/publications/85077940751
U2 - 10.1056/NEJMoa1905633
DO - 10.1056/NEJMoa1905633
M3 - Article
C2 - 31940699
AN - SCOPUS:85077940751
SN - 0028-4793
VL - 382
SP - 256
EP - 265
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 3
ER -