Early onset or syndromic epilepsy
Gene: RNASEH2C
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 3. Vogt et al 2013 - 2 pakistani sisters - no mention of seizures. Muitari et al, 2018 - 2 patients with a hom variant - both 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?? Hebbar et al, 2018 - 3 Indian families (4 individuals - all had seizures and a hom missense variant -thought to be founder mutation.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, 610329
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: Confirmed DD-G2P gene for Aicardi-Goutieres syndrome 3, which can present with seizures. Most AGS patients carry the c.205C>T variant, which has been characterized as Founder effect in Pakistani patients (PMID:29150899). Additional variants are observed in single families (PMID:25604658 and PMID:20131292). Although it's unclear in some papers whether the AGS patients specifically with RNASEH2C variants displayed seizures, RNASEH2C variants are a known cause of AGS, and seizures are a common feature of AGS; therefore it is reasonable to include RNASEH2C on the Genetic Epilepsy panel.Created: 8 Nov 2018, 9:04 a.m.
PMID:29239743 (Mutairi et al., 2018) reviewed the records of 24 unrelated Arab patients with Aicardi-Goutières syndrome. The most common presenting signs were developmental delay and seizures. Homozygous c.205C>T variants in RNASEH2C were found in 2 cases, both of whom had seizures.
Rice et al 2007 (PMID:17846997) collected clinical data for 123 individuals from 94 families with variants in TREX1, RNASEH2A, RNASEH2B, or RNASEH2C. 2 individuals who presented at birth had RNASEH2C variants and experienced neonatal seizures (Table 2).
PMID:25604658 (Crow et al. 2015) reported on 374 patients from 299 families with symptoms including seizures in 140 patients. 35 families had RNASEH2C variants.
PMID:29150899 (Hebbar et al 2018) identify a founder variant (c.205C>T (NM_032193.3, p.Arg69Trp) in RNASEH2C in three Indian families (4 patients) with AGS. All patients had seizures and neurodevelopmental delay. This variants contributes to 72% of cases with AGS type 3. Other variants are observed in single families (PMID:25604658 and PMID:20131292).Created: 8 Nov 2018, 9:02 a.m.
Seizures are part of the phenotype of this neurological disorder.Created: 20 Aug 2018, 10:33 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Aicardi-Goutieres syndrome 3, MIM#610329
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to RNASEH2C.
Source NHS GMS was added to RNASEH2C.
Zornitza Stark: Seizures are part of the pheno
Gene: rnaseh2c has been classified as Green List (High Evidence).
Gene: rnaseh2c has been classified as Green List (High Evidence).
Publications for gene: RNASEH2C were set to
Mode of inheritance for gene: RNASEH2C was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RNASEH2C were changed from to Aicardi-Goutieres syndrome 3, 610329
Expert Review Amber was added to RNASEH2C. Panel: Genetic Epilepsy Syndromes
RNASEH2C was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
RNASEH2C was created by Sarah Leigh