Early onset or syndromic epilepsy
Gene: SIK1
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 EIEE30. Hansen et al, 2015 - 6 unrelated children with early onset refractory epilepsy. 6 diifferent de novo het mutations identified - 3 missense, 3 truncating. In vitro functional expression studies showed all mutant proteins identified even truncating ones = normal kinase activity. Studies in HEK293 cells, showed that missense mutant proteins had normal punctate nucelar localistion, similar to wt, where as truncated proteins had a broader pattern of localisation in the nucleus and cytoplasm as well as increased stability compared to wild type. Further paper from this group - Proschel et al, 2017, functional work to support pathogenicity.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, 616341
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: Mechanism may be activating (G2P), but truncating or missense mutations still relevant.Created: 29 Jan 2016, 5:06 p.m.
Comment on phenotypes: Sourced from G2P and OMIMCreated: 21 Jan 2016, 1:08 p.m.
Comment on mode of inheritance: Confirmed and not on imprinted gene list.Created: 21 Jan 2016, 1:01 p.m.
Source Wessex and West Midlands GLH was added to SIK1.
Source NHS GMS was added to SIK1.
Ellen McDonagh: Comment on mode of inheritance
Victorian Clinical Genetics Services was added to SIK1. Panel: Genetic Epilepsy Syndromes
SIK1 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert Review
SIK1 was created by Sarah Leigh