Early onset or syndromic epilepsy

Gene: RNASEH2B

Green List (high evidence)

A further 37 patients (11.4%) (13 TREX1, one RNASEH2A, nine RNASEH2B, seven RNASEH2C, six SAMHD1, one ADAR) demonstrated neurological features at birth in the absence of obvious systemic features. (PMID:25604658). AR Aicardi Goutieres syndrome 2. row et al 2006 - 18 unrelated families with AGS2 had hom/compund her mutations. Most families European or North African. Crow et al 2014 - 2 Egyptian sibs and an unrelated patient of N African descent hom variant. No mention on OMIM of seizures in these patients - Crow 2015 paper mentions seizures in a number of patients - but don't know if specific gene or across all the AGS genes mentioned in the paper. Mutairi et al, 2018 - 3 diff hom variants in this gene in 13 patients 8/13 had seizures. Approx 42 variants listed on HGMD Pro - missense, nonesense, splicing, small del/ins - mostly assoc with AGS. If seizures is a common phentoype of AGS.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Aicardi-Goutieres syndrome, 610181

Publications

• 25604658

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Comment on list classification: Updated rating from Amber to Green: Confirmed DD-G2P gene for Aicardi-Goutieres syndrome 2 (MIM:610181), which can present with seizures. Sufficient cases of seizures (>3) from PMIDs29239743, 17846997 and 28332073 for inclusion on panel.

Created: 8 Nov 2018, 8:59 a.m.

Abdel-Salam, 2017 (PMID:28332073) report two siblings with AGS, both with seizures among their phenotypes. They
identified a previously known homozygous missense variant in exon 7 of the RNASEH2B gene, c.554T>G (p.V185G), and both parents were heterozygous for the variant.

Created: 8 Nov 2018, 8:56 a.m.

Rice et al 2007 (PMID:17846997) collected clinical data for 123 individuals from 94 families with variants in TREX1, RNASEH2A, RNASEH2B, or RNASEH2C. Seizures were reported in 53% of patients. 47 families harboured a RNASEH2B variant.

Created: 8 Nov 2018, 8:56 a.m.

PMID:29239743 (Mutairi et al., 2018) reviewed the records of 24 unrelated Arab patients with Aicardi-Goutieres syndrome. The most common presenting signs were developmental delay and seizures. 3 different homozygous variants were identified in RNASEH2B in 13 patients; The c.356A>G variant seen in 10 cases is listed as Likely Pathogenic. The c.529G>A and c.554T>G variants in the remaining 3 cases are listed as Pathogenic. 8 of the 13 patients had seizures including 1 patient with the pathogenic c.554T>G variant.

Created: 8 Nov 2018, 8:56 a.m.

Comment on phenotypes: Added Phenotypes suggested by external expert reviwer

Created: 4 Oct 2018, 12:56 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this neurological disorder.

Created: 20 Aug 2018, 10:31 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Aicardi-Goutieres syndrome 2, MIM#610181

Variants in this GENE are reported as part of current diagnostic practice