Early onset or syndromic epilepsy
Gene: HCN1
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
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
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
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: 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.
Source Wessex and West Midlands GLH was added to HCN1.
Source NHS GMS was added to HCN1.
Ellen McDonagh: Comment on mode of inheritance
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to HCN1. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to HCN1. Panel: Genetic Epilepsy Syndromes
HCN1 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert Review
HCN1 was created by Sarah Leigh