Explorations Fonctionnelles Musculaires, Service de Physiologie, Hôpitaux Universitaires de Strasbourg, Strasbourg Cedex, Strasbourg, France.
Université de Strasbourg, Faculté de Médecine, Strasbourg, France.
RMD Open. 2021 Oct;7(3). doi: 10.1136/rmdopen-2021-001824.
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.
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.
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.
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.
从分子水平上探索患有自身炎症综合征患者的表型，该患者被诊断为家族性冷自身炎症综合征 2 型（FCAS-2）。使用小鼠模型探索 Nlrp12 在炎症中的功能。
对患者及其家庭成员分离的 DNA 进行全外显子测序和 Nlrp12 靶向重测序。分析 Nlrp12 缺陷和 Nlrp12 功能正常的小鼠体内和体外炎症模型（尿酸盐晶体依赖性急性关节炎症和尿酸盐晶体诱导的腹膜炎）。
在患者及其健康亲属中发现了一种罕见的错义 NLRP12 变异（c.857C>T，p.P286L）。Nlrp12 缺陷型小鼠表现出全身炎症和嗜中性粒细胞浸润减少。
Nlrp12 在小鼠中介导促炎功能。在人类中，必须根据临床和辅助临床数据谨慎解释 Nlrp12 变异的鉴定，以诊断 FCAS-2。
