Early onset or syndromic epilepsy
Gene: MTR
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. Metabolic phenotype with failure to thrive, with seizures presenting later. Better tested through the metabolic panel. Demoted from Green to Amber.Created: 25 Nov 2019, 8:55 p.m. | Last Modified: 25 Nov 2019, 8:55 p.m.
Panel Version: 1.447
PMID:28666289 (Komulainen-Ebrahim et al., 2017) describe a homozygous MTR p.P1173L variant in a patient with drug-resistant seizures associated with hyperhomocysteinemia and hypomethioninemia.Created: 21 Nov 2019, 3:02 p.m. | Last Modified: 21 Nov 2019, 3:02 p.m.
Panel Version: 1.417
PMID:9683607 (Wilson et al., 1998) report 3 cblG patients, including 2 siblings who presented with neonatal seizures.Created: 21 Nov 2019, 3 p.m. | Last Modified: 21 Nov 2019, 3 p.m.
Panel Version: 1.417
PMID:25526710 (Huemer et al., 2015) summarise clinical features of 13 patients with the cblG defect (caused by defects in MTR): 5/13 had seizures.Created: 21 Nov 2019, 2:53 p.m. | Last Modified: 21 Nov 2019, 2:53 p.m.
Panel Version: 1.417
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. Suggested gene rating: Amber.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Homocystinuria-megaloblastic anemia, cblG complementation type, 250940
Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease associationCreated: 4 Dec 2018, 11:24 a.m.
Comment on publications: added publication to support gene-disease associationCreated: 4 Dec 2018, 11:19 a.m.
Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panelCreated: 3 Dec 2018, 5:08 p.m.
Seizures are part of the phenotype.Created: 16 Aug 2018, 12:20 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Homocystinuria-megaloblastic anemia, cblG complementation type, MIM#250940
Variants in this GENE are reported as part of current diagnostic practice
Gene: mtr has been classified as Amber List (Moderate Evidence).
Source Wessex and West Midlands GLH was added to MTR.
Source NHS GMS was added to MTR.
Zornitza Stark: Seizures are part of the pheno
Gene: mtr has been classified as Green List (High Evidence).
Gene: mtr has been classified as Green List (High Evidence).
Publications for gene: MTR were set to 9453374; 12068375; 9683607; 28666289
Publications for gene: MTR were set to 12068375; 9683607; 28666289
Gene: mtr has been classified as Amber List (Moderate Evidence).
Publications for gene: MTR were set to
Phenotypes for gene: MTR were changed from Homocystinuria-megaloblastic anemia, cblG complementation type, 250940; seizures to Homocystinuria-megaloblastic anemia, cblG complementation type, 250940; methionine synthase deficiency type cblG; seizures
Phenotypes for gene: MTR were changed from to Homocystinuria-megaloblastic anemia, cblG complementation type, 250940; seizures
Mode of inheritance for gene: MTR was changed from to BIALLELIC, autosomal or pseudoautosomal
Expert Review Amber was added to MTR. Panel: Genetic Epilepsy Syndromes
MTR was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
MTR was created by Sarah Leigh