Frequency
The prevalence of otulipenia is not known. At least four cases have been reported in the medical literature.
Causes
Otulipenia is caused by mutations in the OTULIN gene. The protein produced from this gene helps control inflammation. Inflammation can be turned on by a cellular process called ubiquitination, in which molecules called ubiquitin are attached to certain proteins. In particular, signaling pathways that lead to inflammation are stimulated by the attachment of chains of ubiquitin molecules linked end-to-end (linear ubiquitin chains). The OTULIN protein helps control inflammation by removing these linear ubiquitin chains.
OTULIN gene mutations that cause otulipenia lead to production of an OTULIN protein with reduced function. As a result, removal of linear ubiquitin chains is impaired, and signaling pathways that cause inflammation are abnormally active. The excessive inflammation that results causes fever, diarrhea, panniculitis, and the other signs and symptoms of otulipenia.
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- AIPDS
- Autoinflammation, panniculitis, and dermatosis syndrome
- ORAS
- OTULIN-related autoinflammatory syndrome
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
- Damgaard RB, Walker JA, Marco-Casanova P, Morgan NV, Titheradge HL, Elliott PR, McHale D, Maher ER, McKenzie ANJ, Komander D. The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity. Cell. 2016 Aug 25;166(5):1215-1230.e20. doi: 10.1016/j.cell.2016.07.019. Epub 2016 Aug 11. Citation on PubMed or Free article on PubMed Central
- Elliott PR, Komander D. Regulation of Met1-linked polyubiquitin signalling by the deubiquitinase OTULIN. FEBS J. 2016 Jan;283(1):39-53. doi: 10.1111/febs.13547. Epub 2015 Nov 2. Citation on PubMed or Free article on PubMed Central
- Keusekotten K, Elliott PR, Glockner L, Fiil BK, Damgaard RB, Kulathu Y, Wauer T, Hospenthal MK, Gyrd-Hansen M, Krappmann D, Hofmann K, Komander D. OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin. Cell. 2013 Jun 6;153(6):1312-26. doi: 10.1016/j.cell.2013.05.014. Citation on PubMed or Free article on PubMed Central
- Zhou Q, Yu X, Demirkaya E, Deuitch N, Stone D, Tsai WL, Kuehn HS, Wang H, Yang D, Park YH, Ombrello AK, Blake M, Romeo T, Remmers EF, Chae JJ, Mullikin JC, Guzel F, Milner JD, Boehm M, Rosenzweig SD, Gadina M, Welch SB, Ozen S, Topaloglu R, Abinun M, Kastner DL, Aksentijevich I. Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease. Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10127-32. doi: 10.1073/pnas.1612594113. Epub 2016 Aug 24. Citation on PubMed or Free article on PubMed Central
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