Heterozygous TREX1 variants in a neonate with Aicardi-Goutières syndrome type 1: a case report
- 1Department of Neonatology , Neonatal Center, Beijing Children’s Hospital, Capital Medical University , , 100045 ,
- 2Department of Radiology , Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health , , 100045 ,
Abstract
Aicardi-Goutières syndrome type 1 (AGS1) is a rare autosomal recessive inflammatory disorder caused by mutations in TREX1 gene, and is frequently misdiagnosed as congenital or neonatal central nervous system infection because of its overlapping clinical manifestations. We report a 27-day-old male neonate who presented with recurrent fever, a persistent cerebrospinal fluid (CSF) pleocytosis, and poor response to broad-spectrum antimicrobial therapy. Imaging revealed diffuse white matter abnormalities and bilateral basal ganglia calcifications. Extensive microbiological investigations were negative, prompting genetic testing. Whole exome sequencing identified two compound heterozygous variants in TREX1: c.294dup (p.Cys99MetfsTer3) and c.868_885del (p.Pro290_Ala295del), inherited from his mother and father, respectively. Based on the clinical manifestations, neuroimaging findings, and genetic results, a diagnosis of AGS1 was established. Treatment with the Janus kinase inhibitor ruxolitinib reduced the frequency and severity of febrile episodes. However, the patient developed microcephaly, neurodevelopmental delay, and motor impairment in infancy. We reported a rare case of AGS1 associated with two compound heterozygous variants, including c.294dup (p.Cys99MetfsTer3) and c.868_885del (p.Pro290_Ala295del). This case expands the genotypic and phenotypic spectrum of TREX1-associated AGS1 and highlights the importance of considering monogenic interferonopathies in neonates presenting with sterile CSF inflammation, intracranial calcifications, and treatment-refractory fever.
Related
- Hyperphosphatasia With Intellectual Disability (Mabry Syndrome) due to Compound Heterozygous PIGO Variants: First Molecularly Characterized Case in French Guiana: A Case Report and Review of the Literature.
- Novel Compound Heterozygous RECQL4 Pathogenic Variants and Associated Phenotypes in a Chinese Patient With Rothmund-Thomson Syndrome: Case Report and Literature Review.
- Novel Compound Heterozygous CEP152 Variants Associated with Atypical Seckel Syndrome 5 in a Chinese Child: Functional Characterization of a Novel Splice-Site Variant and Expansion of the Genotype-Phenotype Spectrum.
- Compound‐Heterozygous PLVAP Missense Variants Associated With Attenuated Protein‐Losing Enteropathy (DIAR10)
- Netherton syndrome presenting with generalized erythroderma in a preterm neonate: Diagnostic and therapeutic challenges.
BibTeX
@article{luo2026heterozygous,
title = {{Heterozygous TREX1 variants in a neonate with Aicardi-Goutières syndrome type 1: a case report}},
author = {Jie Luo and Xiaojiao Wang and Ying Liu and Jingwen Weng and Huanyu Luo and Mingyan Hei},
journal = {Open life sciences},
year = {2026},
month = nov,
doi = {10.1515/biol-2025-1391},
url = {https://europepmc.org/article/PMC/PMC13725325},
note = {CC BY},
}
RIS
TY - JOUR
TI - Heterozygous TREX1 variants in a neonate with Aicardi-Goutières syndrome type 1: a case report
AU - Jie Luo
AU - Xiaojiao Wang
AU - Ying Liu
AU - Jingwen Weng
AU - Huanyu Luo
AU - Mingyan Hei
PY - 2026
DA - 2026/11/02
JO - Open life sciences
DO - 10.1515/biol-2025-1391
UR - https://europepmc.org/article/PMC/PMC13725325
AB - Aicardi-Goutières syndrome type 1 (AGS1) is a rare autosomal recessive inflammatory disorder caused by mutations in TREX1 gene, and is frequently misdiagnosed as congenital or neonatal central nervous system infection because of its overlapping clinical manifestations. We report a 27-day-old male neonate who presented with recurrent fever, a persistent cerebrospinal fluid (CSF) pleocytosis, and poor response to broad-spectrum antimicrobial therapy. Imaging revealed diffuse white matter abnormalities and bilateral basal ganglia calcifications. Extensive microbiological investigations were negative, prompting genetic testing. Whole exome sequencing identified two compound heterozygous variants in TREX1: c.294dup (p.Cys99MetfsTer3) and c.868_885del (p.Pro290_Ala295del), inherited from his mother and father, respectively. Based on the clinical manifestations, neuroimaging findings, and genetic results, a diagnosis of AGS1 was established. Treatment with the Janus kinase inhibitor ruxolitinib reduced the frequency and severity of febrile episodes. However, the patient developed microcephaly, neurodevelopmental delay, and motor impairment in infancy. We reported a rare case of AGS1 associated with two compound heterozygous variants, including c.294dup (p.Cys99MetfsTer3) and c.868_885del (p.Pro290_Ala295del). This case expands the genotypic and phenotypic spectrum of TREX1-associated AGS1 and highlights the importance of considering monogenic interferonopathies in neonates presenting with sterile CSF inflammation, intracranial calcifications, and treatment-refractory fever.
SN - 2391-5412
ER -