Abstract：
BACKGROUND: NLRP12-associated autoinflammatory disease (NLRP12-AID) is an autosomal dominant autoinflammatory disorder caused by variants of NLRP12 gene. We aimed to report a cohort of Chinese adult patients with NLRP12-AID and summarised phenotypes and genotypes.
METHODS: Twenty patients were diagnosed with NLRP12-AID after performing whole-exome sequencing and were included in our cohort. Demographic information, clinical data and treatment response were collected and evaluated. A literature review of NLRP12-AID was performed, and the clinical features and mutated sites were summarised and compared with our cohort.
RESULTS: Among the 20 NLRP12-AID patients, the main clinical features of NLRP12-AID included fever, cutaneous rash, arthralgia/arthritis, pharyngitis/tonsillitis, lymphadenopathy, myalgia and abdominal pain/diarrhoea. Thirteen NLRP12 variants were detected as F402L, G39V, R1030X, R7G, E24A, Q90X, A218V, A259V, W581X, G729R, R859W, c.-150T>C and c.*126G>C. Glucocorticoids were used in 14 patients, immunosuppressive agents in 13, and tocilizumab in 2. Seventeen patients had good responses to therapy. When compared with 50 NLRP12-AID patients from other countries, Chinese patients had fewer variants in exon 3, higher incidences of cutaneous rash, pharyngitis/tonsillitis and lymphadenopathy. Among all these 70 NLRP12-AID patients, patients carrying non-exon-3 variants had higher frequencies of ocular involvement, pharyngitis/tonsillitis, headache and lymphadenopathy than those with exon-3 variants.
CONCLUSIONS: This is the largest cohort of NLRP12-AID in the world and seven novel variants of NLRP12 were identified. Chinese adult patients of NLRP12-AID had more non-specific symptoms such as pharyngitis/tonsillitis and lymphadenopathy when compared with patients from other countries, for which the less occurrence of exon-3 variants might be one possible reason.
METHODS: Twenty patients were diagnosed with NLRP12-AID after performing whole-exome sequencing and were included in our cohort. Demographic information, clinical data and treatment response were collected and evaluated. A literature review of NLRP12-AID was performed, and the clinical features and mutated sites were summarised and compared with our cohort.
RESULTS: Among the 20 NLRP12-AID patients, the main clinical features of NLRP12-AID included fever, cutaneous rash, arthralgia/arthritis, pharyngitis/tonsillitis, lymphadenopathy, myalgia and abdominal pain/diarrhoea. Thirteen NLRP12 variants were detected as F402L, G39V, R1030X, R7G, E24A, Q90X, A218V, A259V, W581X, G729R, R859W, c.-150T>C and c.*126G>C. Glucocorticoids were used in 14 patients, immunosuppressive agents in 13, and tocilizumab in 2. Seventeen patients had good responses to therapy. When compared with 50 NLRP12-AID patients from other countries, Chinese patients had fewer variants in exon 3, higher incidences of cutaneous rash, pharyngitis/tonsillitis and lymphadenopathy. Among all these 70 NLRP12-AID patients, patients carrying non-exon-3 variants had higher frequencies of ocular involvement, pharyngitis/tonsillitis, headache and lymphadenopathy than those with exon-3 variants.
CONCLUSIONS: This is the largest cohort of NLRP12-AID in the world and seven novel variants of NLRP12 were identified. Chinese adult patients of NLRP12-AID had more non-specific symptoms such as pharyngitis/tonsillitis and lymphadenopathy when compared with patients from other countries, for which the less occurrence of exon-3 variants might be one possible reason.
摘要：
背景：NLRP12相关自身炎性疾病（NLRP12-AID）是由NLRP12基因变异体引起的常染色体显性遗传自身炎性疾病。我们的目的是报告一组中国成人NLRP12-AID患者的表型和基因型。
方法：20例患者在进行全外显子组测序后被诊断为NLRP12-AID，并被纳入我们的队列。人口统计信息,我们收集并评估了临床数据和治疗反应.对NLRP12-AID进行了文献综述，总结了临床特征和突变位点,并与我们的队列进行了比较.
结果：在20名NLRP12-AID患者中，NLRP12-AID的主要临床特征包括发热，皮肤皮疹,关节痛/关节炎，咽炎/扁桃体炎，淋巴结病，肌痛和腹痛/腹泻。检测到13种NLRP12变体为F402L，G39V,R1030X,R7G,E24A,Q90X,A218V,A259V,W581X,G729R,R859W,c.-150T>C和c.*126G>C.14例患者使用糖皮质激素，免疫抑制剂13例，托珠单抗2例。17名患者对治疗反应良好。与来自其他国家的50名NLRP12-AID患者相比，中国患者外显子3变异较少，皮疹发生率较高，咽炎/扁桃体炎和淋巴结病。在所有70名NLRP12-AID患者中，携带非外显子-3变异的患者眼部受累频率较高，咽炎/扁桃体炎，头痛和淋巴结病比外显子-3变异。
结论：这是世界上最大的NLRP12-AID队列，并鉴定了NLRP12的7种新变体。与其他国家的患者相比，中国成年NLRP12-AID患者的非特异性症状更多，例如咽炎/扁桃体炎和淋巴结肿大，其中外显子-3变异体较少出现可能是一个可能的原因。
方法：20例患者在进行全外显子组测序后被诊断为NLRP12-AID，并被纳入我们的队列。人口统计信息,我们收集并评估了临床数据和治疗反应.对NLRP12-AID进行了文献综述，总结了临床特征和突变位点,并与我们的队列进行了比较.
结果：在20名NLRP12-AID患者中，NLRP12-AID的主要临床特征包括发热，皮肤皮疹,关节痛/关节炎，咽炎/扁桃体炎，淋巴结病，肌痛和腹痛/腹泻。检测到13种NLRP12变体为F402L，G39V,R1030X,R7G,E24A,Q90X,A218V,A259V,W581X,G729R,R859W,c.-150T>C和c.*126G>C.14例患者使用糖皮质激素，免疫抑制剂13例，托珠单抗2例。17名患者对治疗反应良好。与来自其他国家的50名NLRP12-AID患者相比，中国患者外显子3变异较少，皮疹发生率较高，咽炎/扁桃体炎和淋巴结病。在所有70名NLRP12-AID患者中，携带非外显子-3变异的患者眼部受累频率较高，咽炎/扁桃体炎，头痛和淋巴结病比外显子-3变异。
结论：这是世界上最大的NLRP12-AID队列，并鉴定了NLRP12的7种新变体。与其他国家的患者相比，中国成年NLRP12-AID患者的非特异性症状更多，例如咽炎/扁桃体炎和淋巴结肿大，其中外显子-3变异体较少出现可能是一个可能的原因。
