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IEMbase 0770: RNASEH2B-related ribonuclease H2 subunit B deficiency

Scope

Field Value
IEMbase ID 770
Nosology 16.3.02.01
Nosology code IEM0027
Gene RNASEH2B
External IDs OMIM:610181; ORPHA:51
Generated mapping AMBIGUOUS; Aicardi_Goutieres_Syndrome and subtype Aicardi-Goutieres syndrome 2
Candidate DisMech targets Aicardi_Goutieres_Syndrome.yaml subtype Aicardi-Goutieres syndrome 2
Review date 2026-07-08

IEMbase phenotype signal

IEMbase labels this autosomal recessive record as RNASEH2B-related AGS2. Its clinical signal closely mirrors classical AGS: cognitive impairment, seizures, feeding difficulty, hepatosplenomegaly, sterile pyrexia, dystonia, sleep disturbance, exaggerated startle, irritability, spasticity, microcephaly, leukodystrophy, cerebral atrophy, intracerebral calcification, and chilblain lesions. Laboratory rows include raised CSF neopterin, CSF lymphocytes, CSF interferon-alpha, interferon-stimulated gene signature, autoantibodies, transaminases, platelets, and a neonatal C26:0 fatty acid row.

DisMech phenotype coverage

Aicardi_Goutieres_Syndrome.yaml includes an explicit Aicardi-Goutieres syndrome 2 subtype with RNASEH2B and MONDO:0012429. The disease-level AGS phenotype set covers the major IEMbase neurologic, inflammatory, cutaneous, and imaging features, including spasticity, developmental delay/regression, seizures, dystonia, hepatosplenomegaly, unexplained fevers, microcephaly, leukodystrophy, cerebral calcification, brain atrophy, CSF lymphocytosis, increased CSF interferon-alpha, chilblains, and autoimmunity. The local entry also records RNASEH2B-specific mechanistic nuance: some RNASEH2B patients are interferon-negative and RNASEH2B-associated neurodegeneration may include non-canonical p53/cGAS distinctions.

Concordance and completeness

Judgement: exact subtype coverage; generated ambiguity reflects duplicate disease-level and subtype-level match keys.

The subtype identity, gene, inheritance, and main phenotype pattern are concordant. The main caveat is biomarker interpretation. IEMbase records interferon signature and CSF interferon-alpha as abnormal across the age bands, while DisMech already preserves evidence that a subset of RNASEH2B cases may be IFN-negative. IEMbase should therefore be used as a phenotype prompt, not as a universal RNASEH2B biomarker assertion.

Curation actions

  • Treat Aicardi_Goutieres_Syndrome.yaml subtype Aicardi-Goutieres syndrome 2 as exact local coverage for IEMbase 0770.
  • Keep the local RNASEH2B-specific IFN-negative caveat; do not flatten the subtype into an always-IFN-positive phenotype.
  • Preserve CSF neopterin, feeding difficulty, sleep disturbance, startle response, platelet, and optional cardiopulmonary/ocular rows as completeness prompts.