Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green.Refers to glioma patients: not a seizure disorder. Demoted from Green to RED.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Refers to glioma patients- not a seizure disorder. Demoted from Green to RED.
Rebecca Foulger commented on gene: IDH2: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green.Refers to glioma patients: not a seizure disorder. Demoted from Green to RED.
Rebecca Foulger commented on gene: IDH2: A number of papers note that IDH1 and IDH2 variants have an established association with preoperative seizures in patients with grade II-IV diffuse gliomas (PMID:29172136, 29288860, 22217666).
Rebecca Foulger commented on gene: IDH2: PMID:24049096 (Nota et al., 2013) report 3 cases, with seizures reported in 2/3. Case 2 was a 9 year old Caucasian girl with tonic-clonic seizures and mosaic IDH2 variants. Case 3 was a Caucasian girl with seizures age 3 months- her seizures responded well to anticonvulsants. The patient died from sudden cardiac arrest age 8, and was found to have a heterozygous IDH2 c.419G>A variant. Germline mosaicism in the mother was suggested to explain the inheritance pattern in this family.
Rebecca Foulger Added comment: Comment on mode of inheritance: Kept Mode of Inheritance as MONOALLELIC based on post-Webex review from Helen Lord. Note that the rating of IDH2 was not discussed on the group Webex (2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy) because IDH2 has a Green rating on the 'Inborn errors of metabolism' panel, and therefore will be Green on the Epilepsy super panel for R59.
Rebecca Foulger Mode of inheritance for gene: IDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rebecca Foulger commented on gene: IDH2: Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded an Amber rating to match the original West Midlands, Oxford and Wessex GLH rating.
Helen Lord reviewed gene: IDH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rebecca Foulger Added comment: Comment on mode of inheritance: The mode of inheritance for IDH2 is currently MONOALLELIC on the 'Intellectual disability' panel, and the 'Inborn errors of metabolism' panel.
Rebecca Foulger Mode of inheritance for gene: IDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Tracy Lester reviewed gene: IDH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal