PT  - JOURNAL ARTICLE
AU  - Dan Lévy
AU  - Alexandre Mariotte
AU  - Aurore DeCauwer
AU  - Cecile Macquin
AU  - Angélique Pichot
AU  - Anne Molitor
AU  - Francois Maurier
AU  - Alain Meyer
AU  - Raphael Carapito
AU  - Philippe Georgel
TI  - Contrasting role of <em>NLRP12</em> in autoinflammation: evidence from a case report and mouse models
AID  - 10.1136/rmdopen-2021-001824
DP  - 2021 Oct 01
TA  - RMD Open
PG  - e001824
VI  - 7
IP  - 3
4099  - http://rmdopen.bmj.com/content/7/3/e001824.short
4100  - http://rmdopen.bmj.com/content/7/3/e001824.full
SO  - RMD Open2021 Oct 01; 7
AB  - Objective To explore at the molecular level the phenotype of a patient suffering an autoinflammatory syndrome which was diagnosed as familial cold autoinflammatory syndrome type 2 (FCAS-2). To explore the functions of Nlrp12 in inflammation using mouse models.Methods Whole exome sequencing and Nlrp12 targeted resequencing were performed on DNA isolated from the patient and her family members. In vivo and ex vivo models of inflammation (urate crystals-dependent acute joint inflammation and urate crystals-induced peritonitis) were analysed in Nlrp12-deficient and Nlrp12-competent mice.Results A rare missense NLRP12 variant (c.857C>T, p.P286L) was identified in the patient and her healthy relatives. Nlrp12-deficient mice exhibit reduced systemic inflammation and neutrophilic infiltration.Conclusion Nlrp12 mediates proinflammatory functions in mice. In humans, the identification of Nlrp12 variants must be cautiously interpreted depending on clinical and paraclinical data to diagnose FCAS-2.