Early onset or syndromic epilepsy

Gene: MTR

I don't know

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

I don't know

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 association

Created: 4 Dec 2018, 11:24 a.m.

Comment on publications: added publication to support gene-disease association

Created: 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 panel

Created: 3 Dec 2018, 5:08 p.m.

Green List (high evidence)

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