Clinical heterogeneity of NLRP12-associated autoinflammatory diseases

作者全名："Li, Yue; Deng, Mengyue; Li, Yulu; Mao, Xiaolan; Yan, Shi; Tang, Xuemei; Mao, Huawei"

作者地址："[Li, Yue; Deng, Mengyue; Li, Yulu; Mao, Xiaolan; Yan, Shi; Mao, Huawei] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Dept Rheumatol & Immunol, Childrens Hosp,Minist Educ,Chongqing Key Lab Child, Chongqing 400014, Peoples R China; [Tang, Xuemei] Chongqing Med Univ, Childrens Hosp, Dept Rheumatol & Immunol, Chongqing 400014, Peoples R China; [Mao, Huawei] Chongqing Med Univ, Childrens Hosp, Chongqing 400014, Peoples R China"

通信作者："Mao, HW (通讯作者)，Chongqing Med Univ, Childrens Hosp, Chongqing 400014, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001014675600001

JCR分区：Q1

影响因子：6.8

年份：2023

卷号：10

期号：3

开始页：1090

结束页：1100

文献类型：Article

关键词：Autoinflammatory diseases; Familial cold autoinflammatory syndrome type 2 (FCAS2); NLRP12-Associated autoinflammatory disease (NLRP12-AID); Nod-like receptor family pyrin domain-containing protein 12 (NLRP12); Nuclear factor-Kappa B (NF-kB)

摘要："Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is one of the critical pattern recognition receptors which participates in the regulation of multiple inflam-matory responses. Mutations in NLRP12 cause exceptionally rare NLRP12-associated autoin-flammatory disease (NLRP12-AID). So far, very few patients with NLRP12-AID have been identified worldwide; therefore, data on the clinical phenotype and genetic profile are limited. In this study, we reported 10 patients who presented mainly with periodic fever syn-drome or arthritis. Next-generation sequencing (NGS) identified 6 heterozygous mutations of NLRP12, including 2 novel null mutations. Of the patients, some with same mutations showed different clinical features. Compared to healthy controls, the increased levels of cytokines were revealed in the patients' plasmas, as well as in the supernatants of patients' cells stim-ulated with lipopolysaccharide (LPS) or tumor necrosis factor-a (TNF-a). The missense muta-tions did not change the protein expression; but decreased level of NLRP12 protein was shown in the null mutations. And in vitro expression assay demonstrated a truncating protein induced by the frameshift mutation. Further functional studies revealed the deleterious effect of mutations on nuclear factor-kappa B (NF-kB) signaling. Both the null and missense mutations impaired their inhibition of NF-kB activation induced by p65. Collectively, this study reported a relatively large NLRP12-AID case series. Our findings expand the clinical spectrum, and rein-force the diversity of genetic mutations and clinical phenotypes. The NLRP12-associated"

基金机构：National Key Research and Development Program of China [2021YFC2702005]; National Natural Science Foundation of China [81971547]; Research Fund for Outstanding Youth Scholar of Chongqing Talents [CQYC201905003]; High-level Medical Reserved Personnel Training Project of Chongqing [2019181]

基金资助正文："Acknowledgements This study was supported in part by the National Key Research and Development Program of China (No. 2021YFC2702005) , National Natural Science Foundation of China (No. 81971547) , the Research Fund for Outstanding Youth Scholar of Chongqing Talents (No. CQYC201905003) , and the High-level Medical Reserved Personnel Training Project of Chongqing (No. 2019181) ."