若年発症サルコイドーシスとＮＯＤ２―本邦報告１０例の遺伝子解析のまとめ―

Abstract

Early-onset sarcoidosis (EOS) is juvenile-onset systemic granulomatosis that mainly affects skin, joints and eyes. Recent discovery of NOD2 mutations in the familial systemic granulomatosis, Blau syndrome, encouraged us to investigate NOD2 mutations in EOS patients reported in Japan. Among 10 cases, heterozygous missense mutations were found in 9 cases; 4 showed R334W that has been typically reported in Blau syndrome, and 5 showed novel H496L, M513T, T605P, N670K, and D382E. All these 6 variants of NOD2 showed increased nuclear factor(NF)-kappaB activity without its ligand, such as muramyl dipeptide. These findings indicate that the majority of EOS cases reported in Japan shows the genetic etiology of NOD2 mutations that cause constitutive NF-kappaB activation.