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

doi:10.3969/j.issn.1673-5501.2021.01.005

摘要/Abstract

摘要： 目的报道1例Aicardi-Goutières综合征(AGS)7型患儿的临床特点,总结国外既往报道病例特点。方法回顾分析1例AGS7型患儿的临床表现、Ⅰ型干扰素刺激基因表达和全外显子(WES)测序结果。检索PubMed数据库、万方数据库及中国知网数据库中IFIH1或MDA5基因突变导致AGS7的病例,总结临床特征和基因突变谱。结果 3岁男孩,因“反复皮疹2年余”就诊,6月龄起病,临床特点包括生长发育落后、肝功能异常、WBC减低、ESR升高、颅内钙化、脑白质病变、肺间质病变、亚临床甲减,干扰素下游分子表达增加,WES测序:IFIH1基因c.1016C>A(p.Ala339Asp),新生杂合突变,诊断AGS7。文献复习共检索到15篇(与本文病例合并后共31例AGS7患儿)。AGS7可表现为肌张力异常、肢体瘫痪、生长发育落后、皮损等,以及血细胞减少、肝酶异常、甲状腺功能异常、颅内钙化、脑白质病变和脑萎缩等辅助检查异常。31例共检出IFIH1基因17个致病突变,其中16个错义突变,1个无义突变,未发现明确的基因型-临床表型相关性。该疾病无自限性。5例(16.1%)死亡,原因为心肺并发症、嗜血细胞综合征、肝衰竭和胰腺炎。结论 AGS7型是Ⅰ型干扰素相关疾病,以生长发育落后以及神经系统、血液系统、甲状腺、肝、脾等多系统和器官受累为特点。

关键词: Aicardi-Goutières综合征7型, Ⅰ型干扰素相关疾病, 临床特点

Abstract: Objective To report a case of Aicardi-Goutières syndrome type 7 (AGS7) in China and summarize the clinical characteristics of cases previously reported in other countries. Methods The clinical manifestations, the expression of type I interferon stimulated genes and results of whole-exome sequencing (WES) were retrospectively analyzed. We searched AGS7 caused by the mutation of IFIH1 or MDA5 in the databases of PubMed, Wanfang and CNKI. Clinical features and gene mutation spectrum were summarized. Results A 3-year-old boy experienced recurrent rash for more than 2 years since age of 6 months. Further assessment identified growth retardation, abnormal liver function, decreased white blood cells, increased erythrocyte sedimentation rate, basal ganglia calcification, leukodystrophy, pulmonary interstitial disease, subclinical hypothyroidism, and increased expression of interferon stimulated genes. WES revealed a de novo, heterozygous mutation in the IFIH1 gene(c.1016C>A, p.Ala339Asp). The diagnosis of AGS7 was made. Our literature review included 15 publications. A total of 31 patients, including our case, were reported. AGS7 could be characterized by myodystonia, paralysis, developmental backwardness, skin lesions, as well as abnormal auxiliary examination results, such as cytopenia, hypohepatia, thyroid dysfunction, intracranial calcification, leukoencephalopathy and encephalatrophy. A total of 17 pathogenic variants were reported in 31 cases, including 16 missense mutations and 1 nonsense mutation. But a well targeted relationship between genotype and phenotype was not found. It is not a self-limited disease. Five patients (15%.1) died of as cardiopulmonary complications, hemophagocytic syndrome, cirrhosis or pancreatitis. Conclusion AGS7 is a type I interferonopathies characterized by regression of development, and involvement of multiple organs, such as nervous system, blood, thyroid gland, liver, spleen and so on.

Key words: Aicardi-Goutières syndrome type 7, Type Ⅰ interferon-related disease, Clinical features

王伟, 全美盈, 王薇, 王长燕, 马明圣, 宋红梅. IFIH1基因突变致Aicardi-Goutières综合征7型1例并文献复习[J]. 中国循证儿科杂志, 2021, 16(1): 61-65.

WANG Wei, QUAN Meiying, WANG Wei, WANG Changyan, MA Mingsheng, SONG Hongmei. A case of Aicardi-Goutières syndrome type 7 in China and literature review[J]. Chinese Journal of Evidence-Based Pediatrics, 2021, 16(1): 61-65.

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