Brief Report: Involvement of TNFRSF11A molecular defects in autoinflammatory disorders.

摘要: Objective Autoinflammatory disorders are caused by a primary dysfunction of the innate immune system. Among these hereditary recurrent fevers, which characterized episodes fever and inflammatory manifestations affecting multiple tissues. Hereditary fevers often lack objective diagnostic criteria, thereby hampering identification disease-causing genes. This study was undertaken to identify gene responsible for fevers. Methods Copy number variations point mutations were sought array-comparative genomic hybridization polymerase chain reaction sequencing, respectively. Serum cytokine levels measured using Luminex technology. The effect TNFRSF11A molecular defects on NF-κB signaling in cells expressing wild-type mutated forms receptor evaluated luciferase assay. Results A patient with congenital anomalies found carry de novo heterozygous complex chromosomal rearrangement encompassing duplication TNFRSF11A, known regulate rodents. We also identified frameshift mutation (p.Met416Cysfs*110) mother daughter isolated fever. associated increased secretion several cytokines (tumor necrosis factor α [TNFα], interleukin-18 [IL-18], IL-1 antagonist, interferon-γ) altered biologic effects signaling. disease patients described herein exhibits striking clinical similarities TNF receptor–associated periodic syndrome, another involving same family (TNFRSF1A). Conclusion The involvement highlights key role this immunity. present results suggest that screening could serve as new test autoinflammatory disorders.