NEMO mutation as a cause of familial occurrence of Behçet's disease in female patients.

Behçet's disease is a chronic, relapsing, multisystem inflammatory disease of unknown etiology. Nuclear factor κB (NF-κB) essential modulator (NEMO) that is required for the activation of NF-κB plays an important role in inflammation. To investigate the role of NEMO in the pathogenesis of Behçet's disease, we analyzed NEMO gene and its expression pattern in tissues in a family with Behçet's disease. We found a heterozygous mutation (1217A> T, D406V) in a 6-year-old girl and her mother. Skewed X-chromosome inactivation was not observed in the peripheral blood mononuclear cells as well as in oral and intestinal mucosa of the patients. Accordingly, there was a significant proportion of peripheral blood monocytes that did not produce sufficient intracellular tumor necrosis factor-α with the stimulation of lipopolysaccharide. Heterozygous NEMO mutation is a cause of familial occurrence of Behçet's disease in female patients.