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IEMbase 0769: TREX1-related 3-prime repair exonuclease 1 deficiency

Scope

Field Value
IEMbase ID 769
Nosology 16.3.01.01
Nosology code IEM0026
Gene TREX1
External IDs OMIM:225750; ORPHA:481662
Generated mapping AMBIGUOUS; Aicardi_Goutieres_Syndrome and subtype Aicardi-Goutieres syndrome 1
Candidate DisMech targets Aicardi_Goutieres_Syndrome.yaml subtype Aicardi-Goutieres syndrome 1
Review date 2026-07-08

IEMbase phenotype signal

IEMbase labels this autosomal recessive record as TREX1-related AGS1, with alternate name Aicardi-Goutieres syndrome type 1 and abbreviation AGS1. The source signal is the classical AGS interferonopathy pattern: cognitive impairment, dystonia, seizures, feeding difficulty, hepatosplenomegaly, sterile pyrexia, sleep disturbance, spasticity, microcephaly, leukodystrophy, cerebral atrophy, intracerebral calcification, chilblain lesions, exaggerated startle, and irritability. Laboratory rows include raised CSF neopterin, CSF lymphocytes, CSF interferon-alpha, interferon-stimulated gene signature, autoantibodies, variably elevated transaminases, low-to-normal neonatal platelets, and a neonatal normal-to-high C26:0 fatty acid row.

DisMech phenotype coverage

Aicardi_Goutieres_Syndrome.yaml is the correct local target. It has an explicit Aicardi-Goutieres syndrome 1 subtype with TREX1 and MONDO:0009165, and the disease-level AGS entry covers the shared clinical phenotype: spasticity, developmental delay or regression, profound intellectual disability, seizures, dystonia, hepatosplenomegaly, unexplained fevers, microcephaly, leukodystrophy, cerebral calcification, brain atrophy, CSF lymphocytosis, increased CSF interferon-alpha, chilblains, autoimmunity, elevated transaminases, and the type I interferon mechanism.

Concordance and completeness

Judgement: exact subtype coverage; generated ambiguity reflects disease-level and subtype-level matches.

The gene, OMIM identity, inheritance, AGS subtype, and major neurologic, cutaneous, inflammatory, and biomarker signal are concordant. DisMech is more mechanistically explicit for TREX1 loss, endogenous nucleic-acid sensing, and type I interferon signaling. IEMbase adds several useful completeness prompts: CSF neopterin, feeding difficulty, sleep disturbance, startle response, and low-to-normal neonatal platelets are not represented as separate local phenotype or biomarker rows. IEMbase also lists optional glaucoma, hypertrophic cardiomyopathy, and pulmonary hypertension; those should not be promoted without source review because they are low-confidence/optional in the IEMbase age table.

Curation actions

  • Treat Aicardi_Goutieres_Syndrome.yaml subtype Aicardi-Goutieres syndrome 1 as exact local coverage for IEMbase 0769.
  • Do not create a standalone TREX1 disease file unless DisMech later decides to split AGS subtypes out of the current subtype model.
  • Preserve CSF neopterin, feeding difficulty, sleep disturbance, startle response, platelet, and optional cardiopulmonary/ocular rows as future phenotype-completeness prompts.