Genetic epilepsy syndromesGene: MTOR
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 and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
AD Smith-Kingsmore syndrome - rare syndrome - seizures are a feature. Smith et al, 2013 - girl with megancephaly and seizures - de novo het missense variant. Baynam et al, 2015- de novo het missense variant in 3 Aboriginal Australian sibs - all had seizures. All 3 had diff dads, therefore ? mum gonadal mosaic. Functional study suggest GOF mutation. Mroske et al, 2015 - de novo het mutation in 2 aff brothers (no mention of seizures) - again suggesting gonadal mosaicism. Moller et al, 2016 - 8 patients (7/8 epilepsy) including an affected mother and daughter and a pair of monozygotic twins - de novo het missense mutations. Moosa et al , 2017 - 2 sibs born of unrelated german parents (no mention of seizures) - de novo variant - testing showed paternal gonadal mosaicism. Gordo et al, 2018 - SKS rare and so far reported in 23 patients where seizures seen in 73.9%). 4 patients from 3 families - 1 had seizures.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Focal cortical dysplasia, type II, somatic,607341; Smith-Kingsmore syndrome,616638
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
Focal cortical dysplasia, type II, somatic 607341
Mode of pathogenicity
Source Wessex and West Midlands GLH was added to MTOR.
Source NHS GMS was added to MTOR.
Ellen McDonagh: De novo somatic variants in th
Victorian Clinical Genetics Services was added to MTOR. Panel: Genetic Epilepsy Syndromes
MTOR was added to Genetic Epilepsy Syndromes panel. Sources: Other,Expert Review Green
MTOR was created by Sarah Leigh