Early onset or syndromic epilepsy

Gene: RNASEH2A

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 4.Muitari et al - 5 patients with a hom variant - only 1 had seizures. Rice et al 2007. Like SAMHD1 mutations reported in Crow et al, 2015 - paper but don't know of the patients with this variant also have seizures?

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, 610333

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. Green Review plus Confirmed DD-G2P gene for Aicardi-Goutieres syndrome 4, which can present with seizures. Seizures is a common (at least 50%) feature of patients with AGS. Although it's hard to trace in papers whether the AGS patients specifically with RNASEH2A variants displayed seizures, RNASEH2A variants are a known cause of AGS, and seizures are a common feature of AGS; therefore it is reasonable to include RNASEH2A on the Genetic Epilepsy panel.

Created: 8 Nov 2018, 11:07 a.m.

Crow et al., 2015 (PMID:25604658) report data for 374 mutation-positive patients from 299 families encompassing all seven known AGS-related genes. 140 of 362 patients had seizures. Biallelic RNASEH2A variants were reported in 14 families.

Created: 8 Nov 2018, 11:06 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. 4 children from 3 families had biallelic variants in RNASEH2A. 1 individual with RNASEH2A variant who was affected at birth experienced neonatal seizures (Table 2).

Created: 8 Nov 2018, 11:06 a.m.

PMID:29239743 (Mutairi et al., 2018) reviewed the records of 24 unrelated patients with Aicardi-Goutières syndrome from 6 tertiary hospitals in different Arab countries. The most common presenting signs were developmental delay and seizures. 5 patients had homozygous c.557G>A RNASEH2A variants, one of which (case 17, Male) had seizures (Table 1).

Created: 8 Nov 2018, 11:06 a.m.

Green List (high evidence)

Seizures are part of the phenotype.

Created: 20 Aug 2018, 10:28 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Aicardi-Goutieres syndrome 4, MIM#610333

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