Rebecca Foulger commented on gene: ATP1A2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is sufficient evidence to rate this gene Green. Kept rating as Green.
Rebecca Foulger edited their review of gene: ATP1A2: 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: Alison Callaway and John Taylor. Suggested gene rating: Amber. ; Changed rating: AMBER
Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green after discussion with Sarah Leigh; Sufficient cases from PMIDs:28058944, 18028407 and 12953268 of patients with familial hemiplegic migraine (FHM) also exhibiting seizures; PMID:28058944 (Prontera et al., 2018) calculate a co-occurrence of ~30%.
Rebecca Foulger commented on gene: ATP1A2: PMID:28058944 (Prontera et al., 2018) performed a review of the comorbidities of familial/sporadic hemiplegic migraine with seizure/epilepsy in patients with CACNA1A, ATP1A2 or SCN1A mutations. For patients carrying ATP1A2 variants, 30.9% of migraine patients also had seizures. Of 180 patients (27 families): 62 patients had epilepsy.
Rebecca Foulger commented on gene: ATP1A2: Vanmolkot et al., 2003 (PMID:12953268) describe novel variants in ATP1A2 in two families with FHM. The M731T mutation was found in a family with pure FHM. The R689Q variant was identified in a family in which FHM and benign familial infantile convulsions partially cosegregate; all available affected family members with FHM, benign familial infantile convulsions, or both, carried the ATP1A2 mutation.
Rebecca Foulger commented on gene: ATP1A2: PMID:18028407 (Deprez et al., 2008) found ATP1A2 variants in 2/20 families (p.Gly900Arg and p.Cys702Tyr). In the two families, 6 variant carriers had the combination of epilepsy and migraine, 2 had only epilepsy, and 6 six had only migraine.
Rebecca Foulger Added comment: Comment on phenotypes: OMIM reports Generalized tonic-clonic seizures in 50% patients with 'Alternating hemiplegia of childhood 1' (MIM:104290) but says seizures are less common in Migraine, familial basilar/Migraine, familial hemiplegic, 2 (OMIM:602481).
Rebecca Foulger commented on gene: ATP1A2: PMID:29610157 (Ueda et al., 2018) report a 12 year old boy with a history of complex partial seizures, ADHD and fine motor difficulty. WES revealed a de novo missense variant in ATP1A2, and a maternally inherited POLG VUS. The authors hypothesize that the ATP1A2 variant contributed to the patient's phenotype.
Rebecca Foulger Added comment: Comment on publications: PMID:9579893 (Terwindt et al., 1997) studied a large Dutch-Canadian family in which familial hemiplegic migraine (FHM) and a benign familial infantile epileptic syndrome concur and partially cosegregate. The genetic basis of the conditions was not finalised. Note that ATP1A2 is on chromosome 1q23.2.
Deb Pal reviewed gene: ATP1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 18028407; Phenotypes: Familial hemiplegic migraine, Epilepsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes