摘要
目的探讨慢性婴儿神经、皮肤、关节综合征(CINCA)的基因突变、临床表型、治疗及预后情况,从而提高本病的诊断率、降低致残率和致畸率。方法回顾性分析本院诊断的10例CINCA综合征患儿的临床表型、辅助检查、治疗及随访情况。经家长同意后取患儿及父母各3 ml EDTA抗凝血,用QIAamp全血DNA提取试剂盒(德国Qiagen公司)提取基因组DNA,应用Agilent液相捕获目标基因技术(Agilent公司)进行全外显子基因检测,最后应用Sanger测序法进行验证。结果本研究共发现CINCA综合征患儿NLRP3基因有8个杂合突变位点,分别是913G/A(D305N)、1057G/T(V353L)、1702T/A(F568I)、1703T/A(F568Y)、1710G/C(K570N)、1789A/G(S597G)、1991T/C(M664T)、2269G/A(G757R)。本病多数于生后半月起病,起病表现主要是荨麻疹样皮疹。10例患儿均可见身材矮小和特殊面容。所有患儿病程中均有不同程度发热和荨麻疹样皮疹,9例患儿有明显的关节炎,9例患儿有中枢神经系统受累的表现。8例患儿存在双耳神经性耳聋,7例患儿出现双眼视神经炎,6例患儿有肝脾和/或淋巴结肿大。淀粉样蛋白A明显升高。糖皮质激素和免疫抑制剂是治疗本病的基本用药,疗效不佳者需早期加用生物制剂缓解病情。结论CINCA综合征是一种罕见的常染色体显性遗传性疾病,以皮肤、关节和中枢神经系统受累为主要表现,可合并脏器淀粉样变性,早期诊断和治疗可以减少重要脏器受累。
Objective To explore the gene mutation, clinical phenotype, treatment and prognosis of chronic infantile neurologic, cutaneous, articular (CINCA) syndrome, so as to improve the diagnosis rate, reduce the disability rate and teratogenicity rate of CINCA syndrome. Methods Ten children with CINCA syndrome admitted to our hospital were retrospectively analyzed in terms of the clinical phenotypes, auxiliary examinations, treatment and follow-up. Three ml ethylene diamine tetraacetic acid (EDTA) anticoagul-ation was taken from children and their parents with the consents. Genomic DNA was extracted by QIAamp whole blood Deoxynbonucleic acid (DNA) extraction kit (German Qiagen Company). The whole exons were detected by Agilent liquid phase capture technology (Agilent Company). Finally, Sanger sequencing was used to verify the results. Results In this study, eight mutations of NLRP3 gene were found in children with CINCA syndrome, namely 913G/A(D305N), 1057G/T(V353L), 1702T/A(F568I), 1703T/A(F568Y), 1710G/C(K570N), 1789A/G(S597G), 1991T/C(M664T), 2269G/A(G757R). The onset age of most of the cases was less than half a month, and the initial manifestation was mainly urticaria-like rash. Short stature and special face could be seen in all 10 cases. All the patients had fever and urticarial rash in varying degrees during the course of the disease. Nine of them had obvious arthritis. Nine children had central nervous system involvement. There were 8 cases of binaural nervous deafness, 7 cases of binocular optic neuritis, and 6 cases of hepato-splenomegaly and/or lymphadenopathy. Amyloid A was significantly increased. Glucocorticoids and immunosup-pressive agents are the basic drugs for the treatment of this disease. If the curative effect was not good, biological agents should be added early to alleviate the disease. Conclusion CINCA syndrome is a rare autosomal dominant hereditary disease, the main clinical manifestations of which are skin, joint and central nervous system involvement, and even amyloidosis of organs. Early di
作者
张俊梅
李彩凤
檀晓华
朴玉蓉
韩彤昕
邝伟英
王江
邓江红
李超
李妍
Zhang Junmei;Li Caifeng;Tan Xiaohua;Piao Yurong;Han Tongxin;Kuang Weiying;Wang Jiang;Deng Jianghong;Li Chao;Li Yan(Department of Rheumatology and Immunology, Beijing Children's Hospital, Capital Medical University/National Center for Children's Health, Beijing 100045, China)
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2019年第8期536-539,共4页
Chinese Journal of Rheumatology
基金
北京市医院管理中心儿科学科协同发展中心专项经费资助(XTCX201819).
