■NLRP3相关的自身炎性疾病(NLRP3-AID)的特征在于NLRP3基因中的功能获得变体。由于在中国很少有文献关注儿科NLRP3-AID,我们旨在阐明中国NLRP3-AID患者的表型和基因型。
■中国三个风湿病中心的NLRP3-AID患者通过全外显子组测序或基因组测序进行基因分型。对所有患者及其父母进行Sanger测序。临床表型,治疗,并对预后进行分析。
■在2014年12月至2022年10月之间招募了9名NLRP3-AID患者,平均随访时间超过30个月。发病年龄中位数为12个月,小于3岁的占66.7%。诊断明显延迟,中位延迟时间为115个月。患者最常出现皮疹(100%),关节炎/关节痛(88.9%),淋巴结肿大(88.9%),发烧(77.8%),和生长迟缓(44.4%)。在急性发作期间,白细胞,C反应蛋白,和/或红细胞沉降率在所有情况下都增加,57.1%的患者(4/7)在发热消退后7天之后炎症标志物仍然升高。2例慢性婴儿神经皮肤关节综合征(CINCA)的手指,一个患有间质性肺病,一个很少报道的发现。糖皮质激素(77.8%)和生物制剂(33.3%)治疗完全缓解66%,部分缓解33%。遗传分析确定了八个致病性NLRP3错义突变,包括一个新的突变。
■我们的研究揭示了中国NLRP3-AID患者的独特临床和遗传特征,强调早期遗传筛查的重要性。尽管诊断延迟,主要用糖皮质激素和生物制剂治疗,导致了有利的结果。遗传异质性,包括一个新的突变,强调了该人群中NLRP3-AID的复杂性。
UNASSIGNED: NLRP3-associated autoinflammatory disease (NLRP3-AID) is characterized by gain-of-function variants in the NLRP3 gene. Since there are little literature focusing on pediatric NLRP3-AID in China, we aimed to elucidate the phenotypic and genotypic profiles of Chinese patients with NLRP3-AID.
UNASSIGNED: Patients with NLRP3-AID at three rheumatology centers in China were genotyped through whole exome sequencing or gene panel sequencing. Sanger sequencing was performed on all patients and their parents. Clinical phenotype, treatment, and prognosis were analyzed.
UNASSIGNED: Nine patients with NLRP3-AID were enrolled between December 2014 and October 2022 with an average follow-up period exceeding 30 months. The median age of onset was 12 months, and 66.7% were younger than 3 years old. The diagnosis was significantly delayed and the median delay duration was 115 months. The patients most commonly presented with rash (100%), arthritis/arthralgia (88.9%), lymphadenopathy (88.9%), fever (77.8%), and growth retardation (44.4%). During acute attack, white blood cell, C-reactive protein, and/or erythrocyte sedimentation rate all increased in all cases, and inflammatory markers remained elevated beyond 7 days postfever resolution in 57.1% of patients (4/7). Two cases of chronic infantile neurological cutaneous articular syndrome (CINCA) had clubbed fingers, one with interstitial lung disease, a finding rarely reported. Treatment with glucocorticoids (77.8%) and biologic agents (33.3%) yielded 66% complete remission and 33% partial remission. Genetic analysis identified eight pathogenic NLRP3 missense mutations, including one novel mutation.
UNASSIGNED: Our study illuminated the distinct clinical and genetic features of Chinese NLRP3-AID patients, emphasizing the significance of early genetic screening. Despite delayed diagnosis, treatment primarily with glucocorticoids and biologic agents, led to favorable outcomes. Genetic heterogeneity, including a novel mutation, highlighted the complexity of NLRP3-AID in this population.