Early onset or syndromic epilepsy

Gene: KCNA2

Comment 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:616366

Created: 21 Apr 2021, 3:53 p.m. | Last Modified: 21 Apr 2021, 3:53 p.m.

Panel Version: 2.328

I don't know

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

Green List (high evidence)

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

• 25751627
• 28032718

Green List (high evidence)

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

Publications

• Syrbe et al (2015) Nat Genet 47(4): 393-9

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

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

Publications

• Syrbe et al (2015) Nat Genet 47(4): 393-9

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

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

Publications

• Syrbe et al (2015) Nat Genet 47(4): 393-9

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

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

Publications

• Syrbe et al (2015) Nat Genet 47(4): 393-9

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.