English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Question Like other disorders with a strong genetic association, a growing sequence dataset from various autoinflammatory syndrome patients continues to identify many variants of uncertain significance (VUS), i.e. missense and intronic variants or small insertions/deletions, for which the impact on protein function and pathways, and therefore the clinical significance, is unknown. Since it is unclear how these variants are associated with an increased risk of autoinflammatory disease, the clinical management of carriers of VUS is complicated. Therefore, there is a strong demand for reliable tests to rapidly assess the clinical significance of VUS, providing carriers of these variants with the necessary information to make an informed clinical decision and refining treatment by stratified therapy strategies. In many cases, a novel VUS is not common enough to evaluate its significance. Common variants with apparently variable penetrance can be more accessible as a model to test functional aspects. A missense variant in TNFRSF1A rs41495584 (“p.R92Q”) is the most commonly identified variant associated with TRAPS within our mainly Caucasian UK patient population. The aim of this study was to comprehensively examine the intracellular signalling pathways that are affected by the presence of p.R92Q, in comparison to normal cells and to wellknown symptomatic variants such as p.C33Y. Methods PBMCs were collected from patients and healthy volunteers with informed consent. Reverse-phase protein microarray was applied to examine a large number of signalling molecules and inflammatory cytokines, using a feature subset selection process to identify distinctive subsets.

pediatric rheumatology online journal

The intracellular signalling pathway signature (the signalome) in PBMCs in the presence of a common TRAPS-associated genetic variant, TNFRSF1A p.(Arg121Gln) (legacy p.R92Q) is distinct from normal PBMCs and from other pathogenic variants