Early onset or syndromic epilepsy

Gene: ARV1

As a result of watchlist tag audit the watchlist tag was removed from ARV1- this is now a green gene with sufficient evidence/review

Created: 13 Jan 2020, 1:28 p.m. | Last Modified: 13 Jan 2020, 1:28 p.m.

Panel Version: 2.0

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)

AR EIEE38. Alzami et al 2015 & Palmer et al 2016 - highly consanguineous Saudi family in which 3 children had EIEE, profound intellectual disability, ataxia and inspecified visual impairment - hom missense variant in all affected, no functional work. Palmer et al, 2016 also reported femal infant of consang Lebanese parents - epilepsy presented at 4 months, died aged 12 months - hom splice site variant. Functional work showed that the aplice variant was unable to rescue a growth defect in arv1-null yeast, whereas the G189R mutation retained some activity. Suggest LOF. Farwell-Hagman - hom splice site variant was identifed in a patient with an undiagnosied neurodevelopmental disorder - classed as the suspected candidate.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, early infantile, 617020

Publications

• 25558065
• 27270415

Green List (high evidence)

Comment on list classification: Taking experimental data into account, there is sufficient evidence for this gene to be green on this panel. PMID 27270415 reported functional studies which demonstrated that the splice site variant c.294+1G-A was unable to rescue a growth defect in arv1-null yeast, whereas the c.565G>A, p.G189R retained some activity. Furthermore, Arv1-null mice had a phenotype that reflected Epileptic encephalopathy, early infantile, 38 617020 and died prematurely PMID 27270415. Gene rating approved by Dr Arianna Tucci (Genomics England Clinical Fellow and Curator).

Created: 23 Jul 2018, 12:30 p.m.

Although only two variants have been reported in two families, supportive in vitro studies are presented together with an animal model, whose phenotype matches the relevant EE.

Created: 17 Jul 2018, 10:05 a.m.

I don't know

Associated with the phenotype in OMIM, two families reported to date, therefore marked as amber and watchlist tag added

Created: 5 Jul 2018, 9:59 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epileptic encephalopathy, early infantile, 38 617020