Early onset or syndromic epilepsy

Gene: GOSR2

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 progressive myoclonic epilepsy 6 - onset of ataxia in first few years of life follwed by action myoclonis and seizures later in childhood. Corbett et al, 2011, 6 patients including 2 sibs - early childhood onset of progressive myoclonic epilepsy - all had seizures of some sort all had the same hom LOF missese variant G144W - haplotype analysis indicate a founder effect. Van Egmond et al, 2014 - 5 additional Dutch patients with EPM6 all had onset betwen the ages of 2-3 and 4/5 developed seizures in the first decade - all hom for G144W. Praschberger et al, 2015 - developed epilepsy around the age of 14, milder course than prev reported patients - compound het for G144W and a novel inframe del. Seizures common feature. Volker et al, 2017 - functional work on G144W and Lys164 del variants.

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
Epilepsy, progressive myoclonic, 614018

Publications

• 21549339
• 30363482

Green List (high evidence)

added founder-effect tag. Even though there is a founder effect in this population, there is further evidence for it being the gene of interest by the fact that there is more than one variant identified so supports a green rating on the current evidence.

Created: 16 Nov 2018, 3:07 p.m.

Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.

Created: 16 Nov 2018, 2:59 p.m.

External review notes that there are Corbett et al., 2011 (PMID: 21549339) reported five unrelated individuals reported with bi-allelic variants and denoted a founder effect.
To date, 17 reported patients with GOSR2‐mediated Progressive myoclonic epilepsy have been shown to carry the same homozygous c.430G>T (p.G144W) mutation, the result of a founder effect 21549339, 23449775, 24458321. However, Praschberger et al., (2015) PMID: 30363482 described a 61‐year‐old female patient suffering from progressive myoclonus epilepsy and was found to be compound heterozygous for the known c.430G>T and a novel c.491_493delAGA (p.K164del) GOSR2 mutation.

Created: 16 Nov 2018, 2:59 p.m.

Comment on publications: Added publications suggested from external expert review and additional publications to support upgrading of the gene to Green

Created: 16 Nov 2018, 1:41 p.m.

Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel

Created: 16 Nov 2018, 9:35 a.m.

Comment on mode of inheritance: added MOI suggested by external review, confirmed with OMIM/publications

Created: 16 Nov 2018, 9:34 a.m.

Green List (high evidence)

Five unrelated individuals reported with bi-allelic variants in this gene, founder effect.

Created: 14 Aug 2018, 11:03 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, progressive myoclonic 6, MIM#614018

Publications

• 21549339

Variants in this GENE are reported as part of current diagnostic practice

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)