Early onset or syndromic epilepsy
Gene: GOSR2
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
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
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 GreenCreated: 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 panelCreated: 16 Nov 2018, 9:35 a.m.
Comment on mode of inheritance: added MOI suggested by external review, confirmed with OMIM/publicationsCreated: 16 Nov 2018, 9:34 a.m.
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
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to GOSR2.
Source NHS GMS was added to GOSR2.
Zornitza Stark: Five unrelated individuals rep
Gene: gosr2 has been classified as Green List (High Evidence).
Tag founder-effect tag was added to gene: GOSR2.
Gene: gosr2 has been classified as Green List (High Evidence).
Publications for gene: GOSR2 were set to 21549339; 30363482; 24458321; 27618868
Publications for gene: GOSR2 were set to 21549339; 30363482; 24458321
Publications for gene: GOSR2 were set to
Phenotypes for gene: GOSR2 were changed from to Epilepsy, progressive myoclonic 6, 614018
Mode of inheritance for gene: GOSR2 was changed from to BIALLELIC, autosomal or pseudoautosomal
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to GOSR2. Panel: Genetic Epilepsy Syndromes
Expert Review Amber was added to GOSR2. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to GOSR2. Panel: Genetic Epilepsy Syndromes
GOSR2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Red,Expert
GOSR2 was created by Sarah Leigh