Genetic epilepsy syndromesGene: KCNT2
Kept rating as Green based on Green post-Webex review from Helen Lord.
Created: 9 Sep 2019, 10:25 a.m. | Last Modified: 9 Sep 2019, 10:25 a.m.
Panel Version: 1.315
Review and rating 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 was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
AD EIEE57. Gururaj et al, 2017 (29069600) - 4 year old boy with intractable seizures ass with developmental regression - misnly prolonged tonic but also had myoclonic jerks and atypicalabsence. De novo het missense variant, F240L. In vitro functional expression studies showed decreased expression of mutant protein as well as signif altered ion selectivity. Ambrosino et al, 2018 (29740868) - 2 unrelated males, both had seizures and both had de novo missense variants R190H and R190P.
Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
KCNT2 identified by external reviewer.
Gururaj et al (PMID:29069600) reported on a male child with early infantile epileptic encephalopathy. Following trio sequencing a de novo hetrozygous variant (NM_001287819.1:c.[720T > A];p.[(Phe240Leu)] was identified in KCNT2. Some functional work was performed on Chinese hamster ovary (CHO) cells and Xenopus laevis oocyte which confirmed that Phe-240 is critical in gating and expression.
Ambrosino et al (PMID:29740868) reported on two female children with de novo variants in KCNT2 one individual with West syndrome followed by Lennox-Gastaut syndrome the other with developmental and epileptic encephalopathies with migrating focal seizures.
Both individuals and their parents underwent sequencing, one individual had a KCNT2 de novo missense variant, c.569G>A, p.(Arg190His) and the other had a KCNT2 de novo missense variant, c.569G>C, p.(Arg190Pro). Some function work on HEK-293 cells were performed.
KCNT2 is included on some diagnostic panels.
KCNT2 has sufficient evidence from (>3) unrelated families and some functional work to support this to be classified as a Green gene.
Created: 4 Jul 2019, 3:17 p.m. | Last Modified: 4 Jul 2019, 3:18 p.m.
Panel Version: 0.55
Source Wessex and West Midlands GLH was added to KCNT2.
Source NHS GMS was added to KCNT2.
Source Expert Review Green was added to KCNT2. Source Expert Review was added to KCNT2. Mode of inheritance for gene KCNT2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes ?Epileptic encephalopathy, early infantile, 57 for gene: KCNT2 Publications for gene KCNT2 were changed from 29740868; 29069600 to 29069600; 29740868 Rating Changed from No List (delete) to Green List (high evidence)
gene: KCNT2 was added gene: KCNT2 was added to Genetic epilepsy syndromes. Sources: Expert list Mode of inheritance for gene: KCNT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNT2 were set to 29740868; 29069600 Phenotypes for gene: KCNT2 were set to epilepsy Penetrance for gene: KCNT2 were set to unknown Review for gene: KCNT2 was set to GREEN gene: KCNT2 was marked as current diagnostic