A case of Aicardi-Goutières syndrome caused by TREX1 gene mutation

Abstract

Aicardi-Goutières syndrome (AGS) is a rare genetic disorder involving the central nervous system and autoimmune abnormalities, leading to severe intellectual and physical disability with poor prognosis. AGS has a phenotype similar to intrauterine viral infection, which often leads to delays in genetic counseling. In this study, we report a case with a prenatal diagnosis of AGS. The first fetal ultrasound detected bilateral lateral ventricle cystic structures, and fetal MRI was performed to identify other signs. The right parietal lobe signal showed cerebral white matter abnormalities, and fetal brain development level was lower than that of normal fetuses of the same gestational age. Whole-exome sequencing revealed that the fetus carried the TREX1:NM_033629.6:exon2:c.294dup:p. C99Mfs*3 variant, suggesting that the c.294dup mutation of the TREX1 gene was the pathogenic mutation site, and the final comprehensive diagnosis was AGS1. In this article, we also reviewed the previous literature for possible phenotypes in the fetus and found that microcephaly and intrauterine growth retardation may be the first and most important markers of the intrauterine phenotype of AGS.

Keywords: Aicardi-Goutières syndrome; Autoimmune diseases of the nervous system; Microcephaly; Nervous system malformations; Prenatal diagnosis; TREX1; Whole-exome genome sequencing.

Fig. 1

Prenatal ultrasound (A) and prenatal fetal MRI (B) showed cystic structures in the posterior horn of the fetal lateral ventricle

Fig. 2

Prenatal fetal MRI showed a short T2 signal in the white matter of the right parietal lobe of the fetus

Fig. 3

Generation verification result information: TREX1:NM_033629.6:exon2:c.294dup:p. C99Mfs*3