Yukiko Takeda, Masahiro Ueki, Junpei Matsuhiro, Erik Walinda, Takayuki Tanaka, Masafumi Yamada, Hiroaki Fujita, Shunichiro Takezaki, Ichiro Kobayashi, Sakura Tamaki, Sanae Nagata, Noriko Miyake, Naomichi Matsumoto, Mitsujiro Osawa, Takahiro Yasumi, Toshio Heike, Fumiaki Ohtake, Megumu K Saito, Junya Toguchida, Junko Takita, Tadashi Ariga, Kazuhiro Iwai
OTULIN-related autoinflammatory syndrome (ORAS), a severe autoinflammatory disease, is caused by biallelic pathogenic variants of OTULIN, a linear ubiquitin-specific deubiquitinating enzyme. Loss of OTULIN attenuates linear ubiquitination by inhibiting the linear ubiquitin chain assembly complex (LUBAC). Here, we report a patient who harbors two rare heterozygous variants of OTULIN (p.P152L and p.R306Q). We demonstrated accumulation of linear ubiquitin chains upon TNF stimulation and augmented TNF-induced cell death in mesenchymal stem cells differentiated from patient-derived iPS cells, which confirms that the patient has ORAS...
June 3, 2024: Journal of Experimental Medicine