OBJECTIVEAicardi-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.

METHODInformation 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 developmental 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.

CONCLUSIONWe 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.