Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 36; pp. 10127 - 10132
• Main Authors: Zhou, Qing, Yu, Xiaomin, Demirkaya, Erkan, Deuitch, Natalie, Stone, Deborah, Tsai, Wanxia Li, Kuehn, Hye Sun, Wang, Hongying, Yang, Dan, Park, Yong Hwan, Ombrello, Amanda K., Blake, Mary, Romeo, Tina, Remmers, Elaine F., Chae, Jae Jin, Mullikin, James C., Güzel, Ferhat, Milner, Joshua D., Boehm, Manfred, Rosenzweig, Sergio D., Gadina, Massimo, Welch, Steven B., Özen, Seza, Topaloglu, Rezan, Abinun, Mario, Kastner, Daniel L., Aksentijevich, Ivona
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 06.09.2016
• Subjects: Age of Onset; Alleles; Biological Sciences; Cells; Child; Child, Preschool; Consanguinity; Cytokines; Cytokines - genetics; Cytokines - immunology; Dermatitis; Dermatitis - physiopathology; Endopeptidases - deficiency; Endopeptidases - genetics; Endopeptidases - immunology; Enzymatic activity; Failure to Thrive - physiopathology; Female; Fever - physiopathology; Fibroblasts - enzymology; Fibroblasts - immunology; Fibroblasts - pathology; Gene Expression Regulation; Genes; HEK293 Cells; Hereditary Autoinflammatory Diseases - diagnosis; Hereditary Autoinflammatory Diseases - enzymology; Hereditary Autoinflammatory Diseases - genetics; Hereditary Autoinflammatory Diseases - pathology; Humans; Leukocytes, Mononuclear - enzymology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - pathology; Male; Molecules; Mutation; NF-kappa B - genetics; NF-kappa B - immunology; Panniculitis - physiopathology; Pedigree; Signal Transduction; Ubiquitin - genetics; Ubiquitin - immunology; linear deubiquitinase; cytokines; autoinflammatory disease; NF-κB pathway; OTULIN

Systemic autoinflammatory diseases are caused by mutations in genes that function in innate immunity. Here, we report an autoinflammatory disease caused by loss-of-function mutations in OTULIN (FAM105B), encoding a deubiquitinase with linear linkage specificity. We identified two missense and one fr...