Early onset or syndromic epilepsy

Gene: HCN1

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)

de novo missense variants, thought to cause a gain of function (PMID: 24747641). AD EIEE 24. Nava et al, 2014 - 6 unrelated patients of European descent - 6 diff het missnese mutations. 5 confirmed de novo. Electrophysiological patch-clamp studies in CHO cells showed divergent effects of the mutations. Some had a major effect on channel gating resulting in a GOF, whereas no current was recorded for others. Marini et al, 2018 - cohort of 33 unpuplisahed patients with novel pathogenic or likely pathogenic variants. 19 probands carrying 14 diff de novo variants and 4 families with dom inherited variants segregating with epilepsy in 14 individuals, but not penetrant in 6 individuals. Functional analysis on 3 variants undertaken.

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, early infantile, 24,615871

Publications

• 24747641
• 25678871

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments

Green List (high evidence)

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

Publications

• Nava et al (2014) Nature Genet 46(6). 640-648

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

• Nava et al (2014) Nature Genet 46(6). 640-648

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

• Nava et al (2014) Nature Genet 46(6). 640-648

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

• Nava et al (2014) Nature Genet 46(6). 640-648

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

Comment when marking as ready: All reviewers agree, and this is a confirmed DD gene for epileptic encephalopathy, early infantile.

Created: 5 Jan 2016, 12:37 p.m.

Comment on phenotypes: Sources: OMIM, G2P.

Created: 5 Jan 2016, 12:36 p.m.

Comment on mode of inheritance: Checked the imprinted gene list, G2P, OMIM.

Created: 5 Jan 2016, 12:35 p.m.