Case Report: Aicardi-Goutières Syndrome Caused by Novel TREX1 Variants

Abstract

TREX1 (three prime repair exonuclease 1) gene encodes DNA 3' end repair exonuclease that plays an important role in DNA repair. Mutations in TREX1 gene have been identified as the cause of a rare autoimmune neurological disease, Aicardi-Goutières syndrome (AGS). Here, we report an AGS case of a 6-month-old Chinese girl with novel TREX1 variants. The patient had mild rashes on the face and legs, increased muscle tensions in the limbs, and positive cervical correction reflex. Cranial magnetic resonance imaging showed that there were patches of slightly longer T1 and T2 signals in the bilateral cerebral hemisphere and brainstem white matter, mainly in the frontotemporal lobe, together with decreased white matter volume, enlarged ventricles, and widened sulcus fissure. Total exon sequencing showed that the TREX1 gene of the child had mutations of c.137_138insC and c.292_293insA, which had not been reported before. In addition, elevated type I interferons were detected by using enzyme-linked immunosorbent assay in the patient's serum. Together, our study demonstrated that novel TREX1 variants (c.137_138insC and c.292_293insA) cause AGS for the first time.

Keywords: Aicardi-Goutières syndrome; Trex1; case report; mutations; type I interferons.

Figure 1

Clinical symptoms of the patient. (A) Mild rashes on the skins of the face and legs. (B) Slightly longer T1 and T2 signals were observed in the frontotemporal white matter, and the volume of white matter was decreased. Ventricles were enlarged, and sulci were widened.

Figure 2

Novel TREX1 mutations and elevated type I IFN were found in the patient. New mutations of c.137 (exon2)_c.138 (exon2) insC (A) and c.292 (exon2)_c.293 (exon2) insA (B) in TREX1 gene of the patient were detected by Trio-based whole-exome sequencing. (C) Increased IFN-α and IFN-β levels in the sera of the patient were detected by ELISA. Statistically significant differences are expressed as ***P < 0.001.