Auto-inflammation in a Patient with a Novel Homozygous OTULIN Mutation
To the editor:
Homozygous mutations in OTULIN (Ovarian TUmor domain deubiquitinases with LINear linkage specificity) result in an auto-inflammation named OTULIN-related auto inflammatory syndrome (ORAS), characterized by prolonged recurrent fevers, joint swelling, gastrointestinal inflammation/diarrhea, failure to thrive, lipodystrophy, and painful erythematous rash with skin nodules [1, 2]. OTULIN deficiency manifests early in life and is potentially lethal.
OTULIN is a deubiquitinase that hydrolyzes linear ubiquitins . Linear ubiquitination regulates various signaling pathways, including the NF-κB pathway. Ubiquitination of NEMO is mediated by Linear UBiquitin chain Assembly Complex (LUBAC). Patients with defects in a LUBAC component develop immunodeficiency and auto-inflammation and die in early childhood [4, 5]. OTULIN counter-regulates LUBAC activity by hydrolyzing linear ubiquitins, thereby avoiding unrestricted NF-κB activation. In the absence of OTULIN, the level of linear...
We kindly thank Saba Arshi, Mohammad Hassan Bemanian, Morteza Fallahpour, Alireza Nateghian, Farhad Abolhasan Chobdar, Davood Mansouri, Mehrnaz Mesdaghi, and Mojgan Kiani Amin for their cooperation and for their help in the work-up of the patient and taking care of the patient. We thank the patient and her family.
This work was supported by a Geconcerteerde Onderzoeksactie (GOA) grant from the Research Council of the Catholic University of Leuven, Belgium.
Whole-exome sequencing, data analysis, and clinical diagnosis were done by Mohammad Shahrooei, Hassan Rokni-Zadeh, and Majid Changi-Ashtiani. Kian Darabi collected the data, Mostafa Manian gathered samples for analyses, and Farhad Seif made substantial contributions to design of the study and edited the draft. Mohammad Nabavi took care of the patient. Isabelle Meyts edited the draft. Jeroen Vrancken and Arnout Voet performed and described the modeling studies. Leen Moens and Xavier Bossuyt designed the experimental studies. Leen Moens performed the experimental analyses. Mohammad Nabavi and Xavier Bossuyt drafted the manuscript. All authors read and approved the manuscript.
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Conflict of Interest
The authors declare that they have no conflicts of interests.
Informed consent was obtained.