Molecular diagnostic yield for Blau syndrome in previously diagnosed juvenile idiopathic arthritis with uveitis or cutaneous lesions

作者全名："Zhong, Zhenyu; Dai, Lingyu; Ding, Jiadong; Gao, Yu; Su, Guannan; Zhu, Yunyun; Deng, Yang; Li, Fuzhen; Gao, Yuan; Yang, Peizeng"

作者地址："[Zhong, Zhenyu; Dai, Lingyu; Gao, Yu; Su, Guannan; Zhu, Yunyun; Deng, Yang; Yang, Peizeng] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China; [Zhong, Zhenyu; Dai, Lingyu; Gao, Yu; Su, Guannan; Zhu, Yunyun; Deng, Yang; Yang, Peizeng] Natl Clin Res Ctr Ocular Dis, Chongqing Branch, Municipal Div, Chongqing, Peoples R China; [Ding, Jiadong; Li, Fuzhen] Zhengzhou Univ, Affiliated Hosp 1, Henan Prov Eye Hosp, Zhengzhou, Peoples R China; [Ding, Jiadong; Li, Fuzhen] Henan Int Joint Res Lab Ocular Immunol & Retinal I, Zhengzhou, Peoples R China; [Gao, Yuan] Third Mil Med Univ, Southwest Hosp, Southwest Eye Hosp, Chongqing, Peoples R China; [Gao, Yuan] Key Lab Visual Damage & Regenerat & Restorat Chong, Chongqing, Peoples R China; [Yang, Peizeng] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Youyi Rd 1, Chongqing 400016, Peoples R China; [Yang, Peizeng] Natl Clin Res Ctr Ocular Dis, Chongqing Branch, Municipal Div, Youyi Rd 1, Chongqing 400016, Peoples R China"

通信作者："Yang, PZ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Youyi Rd 1, Chongqing 400016, Peoples R China.; Yang, PZ (通讯作者)，Natl Clin Res Ctr Ocular Dis, Chongqing Branch, Municipal Div, Youyi Rd 1, Chongqing 400016, Peoples R China."

来源：RHEUMATOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001104683600001

JCR分区：Q1

影响因子：5.5

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Juvenile idiopathic arthritis; Blau syndrome; NOD2; diagnosis; targeted next-generation sequencing

摘要："Objective Diagnostic pitfalls often arise in the community because of potentially misleading similarities between juvenile idiopathic arthritis (JIA) and Blau syndrome, an immune-related disorder caused by NOD2 gene mutations. It remains unclear in which population and to what extent next-generation sequencing techniques can aid in diagnosis.Methods We evaluated clinical usefulness of targeted next-generation sequencing in previously diagnosed JIA. Participants were required to have symptoms and signs suspected of Blau syndrome, including at least uveitis or cutaneous lesions in addition to arthritis. Targeted sequencing was conducted on NOD2 gene to detect diagnostic variants classified as pathogenic or likely pathogenic for Blau syndrome. We assessed the molecular diagnostic yield and clinical implications for patient care.Results Between 1 May 2008 and 1 June 2021, sequencing data were accrued from 123 previously diagnosed JIA (median age: 5 years; female: 62.6%). Targeted NOD2 sequencing yielded a positive molecular diagnosis of Blau syndrome in 21.1% (95% CI: 14.9%, 29.2%), encompassing six heterozygous missense mutations classified as pathogenic variants. Among those receiving a molecular diagnosis, changes in clinical management and treatment were considered as having occurred in 38.5%. Nine predictors were identified as being associated with a higher diagnostic yield, providing clinical clues to suspect the possibility of Blau syndrome.Conclusion Among some patients with paediatric-onset arthritis complicated with uveitis or cutaneous lesions, reassessment of the diagnosis of JIA may be warranted. Targeted NOD2 sequencing established the molecular diagnosis of Blau syndrome in nearly one-fifth of these cases and provided clinically relevant information for patient-care decisions."

基金机构：National Natural Science Foundation Major International (Regional) Joint Research Project [81720108009]; National Natural Science Foundation Key Program [81930023]; Chongqing Key Project [CSTC2021jscx-gksb-N0010]; Chongqing Outstanding Scientists Project; Chongqing Chief Medical Scientist Project; Chongqing Science & Technology Platform and Base Construction Program [cstc2014pt-sy10002]; Chongqing Key Laboratory of Ophthalmology (CSTC) [2008CA5003]; China National Postdoctoral Program for Innovative Talents [BX20230450]

基金资助正文："The work was supported by National Natural Science Foundation Major International (Regional) Joint Research Project (81720108009), National Natural Science Foundation Key Program (81930023), Chongqing Key Project (CSTC2021jscx-gksb-N0010), Chongqing Outstanding Scientists Project (2019), Chongqing Chief Medical Scientist Project (2018), Chongqing Science & Technology Platform and Base Construction Program (cstc2014pt-sy10002), Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003), and China National Postdoctoral Program for Innovative Talents (BX20230450)."