Early onset or syndromic epilepsy
Gene: RNASEH2A
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
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.
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
Source Wessex and West Midlands GLH was added to RNASEH2A.
Source NHS GMS was added to RNASEH2A.
Zornitza Stark: Seizures are part of the pheno
Gene: rnaseh2a has been classified as Green List (High Evidence).
Gene: rnaseh2a has been classified as Green List (High Evidence).
Publications for gene: RNASEH2A were set to
Mode of inheritance for gene: RNASEH2A was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RNASEH2A were changed from to Aicardi-Goutieres syndrome 4, 610333
Expert Review Amber was added to RNASEH2A. Panel: Genetic Epilepsy Syndromes
RNASEH2A was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
RNASEH2A was created by Sarah Leigh