摘要目的 探讨一个Aicardi-Goutières综合征(AGS)家系的临床及影像学特点,并检测其致病基因的突变情况,结合文献总结AGS综合征的临床及基因突变特点.方法 收集2013年1月于北京大学第一医院儿科神经病房住院的一个AGS家系的临床资料,采用DNA直接测序对致病基因行突变检测.在Pubmed、OVID、CNKI、万方等医学文献数据库,采用“Aicardi-Goutières syndrome”或“Aicardi-Goutières综合征”为关键词检素1984年1月至2014年7月文献.并对已报道的252例AGS病例进行复习.结果 (1)临床特点:先证者男,6岁7个月,自幼智力运动发育落后,1岁时发现患儿姿势异常表现为四肢扭转,运动时明显.阳性体征:四肢末端较多冻疮,头围小(47.5 cm),活动时有明显肌张力不全.头颅CT示多发钙化,基底节为著;头颅MRI示脑白质长T1W、长T2W信号,颞叶皮质下白质可见囊性变.先证者妹妹发育正常,面部及四肢末梢可见冻疮,头颅CT示多发钙化,基底节为主.(2)基因突变分析:先证者及其妹妹TREX1发现两个突变,c.294_295insA为未报道的无义突变,c.868_885del为已知致病突变.(3)文献总结:AGS常见的表现包括发育落后[92％(231/252)],肌张力不全[75％(189/252)],小头畸形[63％(159/252)]、冻疮[42％ (106/252)]、基底节钙化[100％(252/252)]、脑萎缩[88％ (222/252)]及脑白质病变[86％(217/252)].在AGS6个致病基因中以TREX1[38％ (96/252)]和RNASEH2B[23％(58/252)]突变较为常见.结论 明确了该AGS家系中的致病基因为TREX1基因突变,为该家庭进行准确的遗传咨询提供了可能.c.294_295insA为未报道的无义突变.

abstractsObjective Aicardi-Goutières syndrome (AGS) is a rare early-onset genetic encephalopathy.The aim of this study was to explore the clinical,imaging and genetic features of a family with AGS,which may contribute to definite diagnosis,genetic counseling and prenatal diagnosis of this rare disease in China.We summarized the characteristics of AGS through reviewing related references.Method Information of the proband and other family members as well as their DNA samples were collected.All the exons and exon-intron boundaries of pathogenic genes were amplified with PCR and were directly sequenced for genomic DNA.And we reviewed the reports of 252 cases.Result (1) The proband was a 6 years plus 7 months old boy.He presented with severe developmmental delay and abnormal posture mainly as torsion of limbs.By physical examination he was found to have some chilblain-like skin lesions at the end of limbs and microcephaly.The CT scan of his head displayed multiple calcification,especially in the basal ganglia.The MRI of his head displayed a hypointense signal in T1-weighted (T1W) images and a hyperintense signal in T2-weighted (T2W) in cerebral white matter and cystic lesions in temporal white matter.The younger sister of the proband presented with chilblain-like skin lesions on her face and the end of limbs had no developmental delay.The CT of her head showed multiple calcification,especially in the basal ganglia.(2) Two mutations were identified in TREX1,one was a novel nonsense mutation (c.294_295insA),and the other was a known pathogenic mutation (c.868_885del).(3) The common performances of AGS included mental retardation [92％ (231/252)],dystonia [75％ (189/252)],microcephaly [63％ (159/252)],chilblain [42％ (106/252)],basal ganglia calcification [100％ (252/252)],brain atrophy [88％ (222/252)] and cerebral white matter lesions [86％ (217/252)].TREX1 [38％ 96/252)] and RNASEH2B [23％ (58/252)] are the most common pathogenic genes.Conclusion We determined pathogenic gene of these patients which is the basis of genetic counseling for this family.c.294_295insA mutation is a novel mutation not reported around the world yet.