Early onset or syndromic epilepsy
Gene: KCNA2Comment on mode of pathogenicity: Both dominant negative variants that result in LOF effect (RCV000170511, rs786205231) and GOF variants (rs786205231, rs786205232) have been associated with Developmental and epileptic encephalopathy 32 OMIM:616366Created: 21 Apr 2021, 3:53 p.m. | Last Modified: 21 Apr 2021, 3:53 p.m.
Panel Version: 2.328
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 EIEE 32. Pena and Coimbra, 2015 - het de novo mutation in affected boy. Syrbe et al, 2015 - 7 unrelated patients - 4 diff de novo het missense variants identified. In vitro functional studies showed 2 of the variants LOF with dom-neg effect, and other 2 - significant GOF and permanently opened channels with a dom effect. The dom GOF patients had a more severe phenotype. Masnada et al, 2017 - cohort of 23 patients (8 prev described) with EIEE carrying wither known or novel KCNA2 variants. 20 of these shown to be de novo. Functional studies also done.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
Phenotypes
Epileptic encephalopathy,616366
Publications
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment when marking as ready: Loss of function and gain of function variants within this gene can cause epileptic encephalopathy (G2P database).Created: 20 Jan 2016, 12:12 p.m.
Comment on phenotypes: Sourced from OMIM and G2P.Created: 20 Jan 2016, 12:11 p.m.
Gene added in expert review of the panel by Richard Scott (Genomics England), Manju Kurian (UCL-Institute of Child Health), Natalie Trump (NHS - Great Ormond Street Hospital), Amy McTague (UCL Institute of Child Health).Created: 12 Nov 2015, 4:14 p.m.
Mode of pathogenicity for gene: KCNA2 was changed from None to None
Phenotypes for gene: KCNA2 were changed from Epileptic encephalopathy, early infantile, 32; EPILEPTIC ENCEPHALOPATHY to Developmental and epileptic encephalopathy 32 OMIM:616366; developmental and epileptic encephalopathy, 32 MONDO:0014607
Publications for gene: KCNA2 were set to Syrbe et al (2015) Nat Genet 47(4): 393-9
Source Wessex and West Midlands GLH was added to KCNA2.
Source NHS GMS was added to KCNA2.
Ellen McDonagh: Gene added in expert review of
Victorian Clinical Genetics Services was added to KCNA2. Panel: Genetic Epilepsy Syndromes
KCNA2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review,Expert Review Green
KCNA2 was created by Sarah Leigh