Epileptic encephalopathy

Gene: MTOR

Green List (high evidence)

Comment on list classification: Promoted from Amber to Green due to ID panel review there is enough evidence to support MTOR and Focal cortical dysplasia, type II . Helen Brittain (Genomics England Curator) Comment on mode of pathogenicity: Note: only missense variants have been reported to date. The relevant spectrum of variants may be limited (? consistent with gain of function). The pick up re somatic mosaic variants is likely to be limited (re focal cortical dysplasia phenotype) however if detected, they could be of clinical relevance. 5 Mar 2018, 12:14 p.m.

Created: 5 Mar 2018, 4:24 p.m.

De novo somatic variants in this gene have been reported in brain tissue of patients with seizures due to focal cortical dysplasia type 2 in more than 6 patients (PMID: 26018084;27830187;25878179). PMID:27830187 also reports an inherited variant identified in a mother-daughter pair with nonlesional autosomal dominant nocturnal frontal lobe epilepsy. Functional in vitro studies in PMID: 26018084 indicate that the mechanism of action may be activating somatic mutations.

Created: 22 Sep 2017, 1:19 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Focal cortical dysplasia, type II, somatic 607341

Publications

• 26018084
• 27830187
• 25878179

Mode of pathogenicity
Other