Rebecca Foulger edited their review of gene: RNASEH2C: Added comment: 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. ; Changed rating: AMBER
Rebecca Foulger commented on gene: RNASEH2A: 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).
Rebecca Foulger Added comment: 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.
Rebecca Foulger commented on gene: RNASEH2B: 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.
Rebecca Foulger commented on gene: TREX1: Rice et al 2007 (PMID:17846997) collected clinical data for 123 individuals from 94 families with variants in TREX1, RNASEH2A, RNASEH2B, or RNASEH2C. Five individuals with TREX1 biallelic variants experienced neonatal seizures (Table 2).