Early onset or syndromic epilepsy

Gene: SCN3A

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 EIEE62 and familial focal epilepsy 4 (FFEVF4). EIEE62: Zaman et al, 2018 - in 4 unrelated epilepsy patients, identifed 3 diff de novo het missense mutations. Whole cell voltage clamp electrophysiological recordings showed the mutant channel had an increase of a slowly inactivating/noninactivating persistent current compared to controls - GOF. FFEVF4: Vanoye et al, 2014 - 4 unrelated patients - 4 diff het missense mutations (genetic screening in 179 pediatric epilepsy patients). In vitro functional expression showed that the variants caused variablew defects of channel function with only some altering the activation and/or inactivation kinetics, however all variants resulted in increased inward currents during a slow depolarising voltage ramp, indicating channel dysfunction capable of enhanicng the response to subthreshold depolarising inputs and promoting hyperexcitability networks. Lamar et al, 2017 - de novo het missense variant, In vitro studies showed it had not detectable sodium current resulting from significant reduction of mutant SCN3A at the cell surface.

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
Epilepsy familial focal with variable foci, 617935 AD; Epileptic encephalopathy early infantile, 617938

Publications

• 28235671
• 29466837

Green List (high evidence)

Comment when marking as ready: Associated with relevant phenotypes in OMIM and as probable Gen2Phen gene for focal epilespy. At least 4 variants have been reported in 4 cases of Epilepsy, familial focal, with variable foci 4 617935 and 3 variants in 4 cases.

Created: 31 Jul 2018, 10:36 a.m.

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

Phenotypes
Epilepsy, familial focal, with variable foci 4 617935; Epileptic encephalopathy, early infantile, 62 617938

Publications

• 24157691
• 29466837
• 28235671