Sarrabay Guillaume, Grandemange Sylvie, Touitou Isabelle
Laboratoire de génétique des maladies rares et auto-inflammatoires, CHRU, Montpellier, France.
Expert Rev Clin Immunol. 2015;11(7):827-35. doi: 10.1586/1744666X.2015.1047765. Epub 2015 May 15.
Cryopyrin-associated periodic syndrome are rare autosomal dominantly inherited diseases. They include three overlapping phenotypes: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem autoinflammatory syndrome (NOMID/CINCA). Recurrent fevers, joint pain, and urticarial skin rash are the main clinical features of these conditions. Renal amyloidosis and sensorineural complications may occur. Gain-of-function mutations in NLRP3 gene are responsible for the overactivation of the NLRP3 inflammasome, a multimolecular complex involved in the inflammatory process. Missense mutations are almost always encountered, particularly in exon 3, which encodes the nucleotide-binding domain. Mosaicism is not rare, especially in CINCA/NOMID. Next-generation sequencing will grant access to new insights about NLRP3 implication in oligogenic and multifactorial diseases.
冷吡啉相关周期性综合征是罕见的常染色体显性遗传病。它们包括三种重叠的表型：家族性冷自身炎症综合征、穆克-韦尔斯综合征以及慢性婴儿神经皮肤关节综合征/新生儿期起病的多系统自身炎症综合征（NOMID/CINCA）。反复发热、关节疼痛和荨麻疹样皮疹是这些病症的主要临床特征。可能会出现肾淀粉样变性和感觉神经性并发症。NLRP3基因的功能获得性突变导致NLRP3炎性小体过度激活，NLRP3炎性小体是一种参与炎症过程的多分子复合物。几乎总是会遇到错义突变，尤其是在编码核苷酸结合域的第3外显子中。嵌合体并不罕见，特别是在CINCA/NOMID中。新一代测序将有助于深入了解NLRP3在寡基因和多因素疾病中的作用。
