Genetic epilepsy syndromesGene: KCNH5
Kept rating as Red based on Red post-Webex review from Helen Lord.
Created: 9 Sep 2019, 10:24 a.m. | Last Modified: 9 Sep 2019, 10:24 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
1 case reported on OMIM - missense change R327H in a boy who developed intractable tonic clonic seizures - Veeramah et al, 2013 (23647072). Structural modelling by Yang et al, 2013 (24133262) suggests it would destabilise the resting and early activation states of the KCNH5 channel by weakening ionic interactions and this favouring channel opening (GLF) - OMIM say it is a VUS as its contribution to epileptic encephalpathy is not confirmed. No other cases in HGMDPro.
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
There is currently only one paper implicating KCNH5 in epilepsy, but it is included on a diagnostic panel (Amplexa CHE-114 epilepsy panel ). Veeramah et al (PMID:23647072) identified an individual with a hetrozygous denovo missense mutation (c.980G>A or p.R327H). However no further disease gene implications have been reported since.
Created: 4 Jul 2019, 12:30 p.m. | Last Modified: 8 Jul 2019, 2:47 p.m.
Panel Version: 0.62
Amplexa CHE-114 epilepsy panel
Sources: Expert list
Created: 21 Feb 2019, 2:05 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to KCNH5.
Source NHS GMS was added to KCNH5.
Publications for gene: KCNH5 were set to 23647072
Source Expert Review Red was added to KCNH5. Mode of inheritance for gene KCNH5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes epilepsy for gene: KCNH5 Rating Changed from No List (delete) to Red List (low evidence)
gene: KCNH5 was added gene: KCNH5 was added to Genetic epilepsy syndromes. Sources: Expert list Mode of inheritance for gene: KCNH5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNH5 were set to 23647072 Phenotypes for gene: KCNH5 were set to epilepsy Penetrance for gene: KCNH5 were set to unknown Review for gene: KCNH5 was set to RED gene: KCNH5 was marked as current diagnostic