Genetic epilepsy syndromesGene: SLC1A2
hom variant reported in PMID 28915517 - can't access full paper to see anymore details
Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Comment on mode of inheritance: Kept Mode of Inheritance as 'BOTH monoallelic and biallelic' based on post-Webex review by Helen Lord.
Created: 7 Sep 2019, 12:03 p.m. | Last Modified: 7 Sep 2019, 12:03 p.m.
Panel Version: 1.297
Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.
Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
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 EIEE41. EPI4K consortium 2016, 2 unrealted girls with EIEE41 2 diff de novo het missense variants). Also noted that the EPI4L project, 2013 - reported another girl with EIEE41 (de novo missense - one of the ones reported in 2016, are these the same patient?). Guella et al, 2017 - 2 unrelated boys with EIEE41 (both had de novo het missense variants. No functional studies done. Wagner et al, 2018, novel hom splicing variant - functional studies on the cDNA level confirmed a LOF.
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
Epileptic encephalopathy, early infantile, 617105
changed rating from amber to green
Created: 6 Dec 2017, 4:54 p.m.
PMID:28915517 (2017) showed that mutations in SLC1A2 are related to epileptic seizures, SLC1A2-related epilepsy is not only caused by heterozygous de novo mutations but can also be inherited in an autosomal recessive fashion, and the genetic mechanism of autosomal dominant SLC1A2-related epileptic encephalopathy is other than haploinsufficiency.
Created: 6 Dec 2017, 4:52 p.m.
Comment on list classification: changed from amber to green, more than missense variants identified, a novel homozygous splicing variant PMD: 28915517. A mouse model also shows that complete lack of protein expression leads to a phenotype including epileptic encephalopathy, which is fatal in many cases PMIDs: 25834045; 9180080
Created: 6 Dec 2017, 3:48 p.m.
Comment on mode of inheritance: recent paper PMID:28915517 suggest that not only de novo mutations but also biallelic variants in SLC1A2 can cause epilepsy and that there is an additional autosomal recessive mode of inheritance.
Created: 6 Dec 2017, 3:40 p.m.
Four unrelated cases with Epileptic encephalopathy, early infantile, 41 (EIEE41) PMID: 27476654, 28777935. Gene added via ID panel update, this gene is more relevant on this panel. In vitro functional studies of the variants and studies of patient cells were not performed, but it has been postulated a toxic gain-of-function effect, perhaps related to glutamate toxicity (PMID:28777935). Only missense variants have been reported in OMIM.
Created: 6 Dec 2017, 3:20 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Epileptic encephalopathy, early infantile, 41, 617105
Gene: slc1a2 has been classified as Green List (High Evidence).
Mode of inheritance for gene: SLC1A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Source Wessex and West Midlands GLH was added to SLC1A2.
Source NHS GMS was added to SLC1A2.
Louise Daugherty: Four unrelated cases with Epil
Victorian Clinical Genetics Services was added to SLC1A2. Panel: Genetic Epilepsy Syndromes
SLC1A2 was added to Genetic Epilepsy Syndromes panel. Sources: Literature,Expert Review Green
SLC1A2 was created by Sarah Leigh