Incomplete penetrance of NOD2 C483W mutation underlining Blau syndrome

Background: Blau syndrome (BS) is a rare autoinflammatory disorder with NOD2 gain-of-function mutation and characterized by autoactivation of the NF kappa B pathway. Classically considered a disease of high penetrance, reports on NOD2 mutations underlining BS with incomplete penetrance is limited. Case presentation: The proband is a 9-year-old girl presented with brownish annular infiltrative plaques and symmetric boggy polyarthritis over bilateral wrists and ankles. Her skin biopsy revealed noncaseating granulomas inflammation with multinucleated giant cells. A novel C483W NOD2 mutation was identify in the proband and her asymptomatic father. Functional examinations including autoactivation of the NF kappa B pathway demonstrated by in vitro HEK293T NOD2 overexpression test as well as intracellular staining of phosphorylated-NF kappa B in patient's CD11b(+) cells were consistent with BS. Conclusions: We reported a novel C483W NOD2 mutation underlining BS with incomplete penetrance. Moreover, a phosphorylated-NF kappa B intracellular staining assay of CD11b(+) was proposed to assist functional evaluation of NF kappa B autoactivation in patient with BS.

Automated summary

This study reported a novel C483W NOD2 mutation associated with incomplete penetrance of BS. Additionally, a new intracellular staining assay of phosphorylated-NF kappa B in CD11b(+) cells was proposed to evaluate NF kappa B autoactivation in patients with BS.