IFIH1基因突变致Aicardi-Goutières综合征7型1例并文献复习  

A Case Report of Aicardi-Goutières Syndrome Type 7 Caused by IFIH1 Gene Mutation and a Literature Review

作　　者：赵敏[1] 舒洲 韩彤昕[2] 付艳华 高天霁 毛华伟 ZHAO Min;SHU Zhou;HAN Tongxin;FU Yanhua;GAO Tianji;MAO Huawei(Department of Rheumatology and Immunology,Baoding Hospital of Beijing Children′s Hospital,Capital Medical University,Baoding 071051,China;Department of Immunology,Beijing Key Laboratory for Genetics of Birth Defects,National Center for Children′s Health,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China;Ministry of Education Key Laboratory of Major Diseases in Children,Beijing Key Laboratory for Genetics of Birth Defects,National Center for Children′s Health,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China)

机构地区：[1]首都医科大学附属北京儿童医院保定医院风湿免疫内科,保定071051 [2]国家儿童医学中心,首都医科大学附属北京儿童医院免疫科,北京100045 [3]国家儿童医学中心,首都医科大学附属北京儿童医院儿科重大疾病研究教育部重点实验室,出生缺陷遗传学研究北京市重点实验室,北京100045

出　　处：《罕见病研究》2024年第4期453-460,共8页Journal of Rare Diseases

基　　金：国家重点研发计划(2022YFC2703100,2021YFC2702005);北京市医院管理中心“登峰”计划(DFL20221001)。

摘　　要：目的探讨IFIH1基因突变导致Aicardi-Goutières综合征(AGS)7型的临床特征和基因突变特点。方法分析1例AGS 7型患儿的临床特征及基因突变结果,回顾性分析文献报道的AGS 7型IFIH1基因突变特点及临床特征。结果本文报道1例13岁男孩,3岁时出现步态异常,逐渐加重并出现双下肢截瘫,病初头颅MRI并无病灶,多年康复治疗并无改善。近期头颅CT发现颅内多发钙化,全外显子组测序发现IFIH1基因杂合突变c.2159G>A(p.R720Q),为已报道的致病性突变。通过文献检索,本文分析AGS 7型的患者69例(包括本文患者)的临床特点,皮肤和神经系统受累最常见。69例患者携带30种IFIH1基因突变,皆为错义突变,其中7例患者基因突变与本文报道病例一致,但临床特点不同。治疗方面,常使用Janus激酶(JAK)抑制剂,近期有托珠单抗治疗本病的报道。结论AGS 7型为Ⅰ型干扰素病,生长发育落后和神经系统受累最常见,并可累及皮肤、血液系统、消化系统、肾脏、心脏等多脏器及系统。JAK抑制剂对本病有一定疗效。Objective To explore the clinical and genetic features of Aicardi-Goutières syndrome(AGS)caused by IFIH1 gene mutation.Methods We analyzed the clinical features and genetic mutation results of a boy with AGS type 7 and conducted a retrospective review of the literature of the characteristics and clinical features of IFIH1 gene mutations in AGS type 7.Results In the case of this report,the patient,13-year-old boy,exhibited gait abnormalities at age 3.As the condition was progressive,the boy has paraplegia of the lower limbs.The first brain MRI showed no lesions.Rehabilitation therapy in the past several years has shown no improvement.Recent brain CT revealed multiple intracranial calcifications.The whole-exome sequencing identified a heterozygous mutation in the IFIH1 gene(c.2159G>A,p.R720Q)-a known pathogenic mutation.Through review of the literature,we identified 69 cases of AGS type 7(including the case reported here)which showed that skin and neurological system involvement are most commonly seen.Among these 69 patients,there were 30 different mutations in the IFIH1 gene,all of which are missense mutations.Seven patients had the same gene mutation as the boy in this study does,but their clinical features differed.In terms of treatment,Janus kainase(JAK)inhibitors are commonly used.Additionally,recent reports showed that tocilizumab treatment have been used for this condition.Conclusions AGS7 is a type of I interferonopathy.Growth retardation and nervous system involvement are the most prevalent.The condition usually involve the skin,blood system,digestive system,kidney,heart,and other organs.JAK inhibitors prove effective for this disease.

关 键 词：Aicardi-Goutières综合征 IFIH1基因 基因突变 罕见病 

分 类 号：R725[医药卫生—儿科]