Skeletal muscle channelopathy
Gene: SLC1A3
The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 3:16 p.m. | Last Modified: 1 Feb 2023, 3:16 p.m.
Panel Version: 2.4
Comment on list classification: Leaving rating as Green but with a recommendation for review by the GMS test evaluation group as to suitability for this panel. Variants seem to result in a brain channelopathy rather than a skeletal muscle one.Created: 9 Jun 2021, 2:54 p.m. | Last Modified: 20 Jul 2021, 2:06 p.m.
Panel Version: 1.31
3 reports in the literature of variants in this gene associated with Episodic ataxia, type 6. These reports suggest a brain channelopathy rather than a skeletal muscle channelopathy.
PMID: 16116111 - Jen et al 2005 - report a 10 yo patient with episodic ataxia, seizures, migraine, and alternating hemiplegia who was found to have a heterozygous mutation in SLC1A3 through screening of this gene. Functional studies in mammalian cell lines showed decreased glutamate uptake, which can contribute to neuronal hyperexcitability.
PMID: 19139306 - de Vries et al 2009 - following analysis of SLC1A3 they report a 35 year old, who has had episodes of ataxia since early childhood, with a heterozygous c.556 T>A (C186S) variant. Nausea, vomiting, photophobia, phonophobia, vertigo, diplopia, slurred speech, and blurred vision often also occur with attacks. His carrier mother and sister were also affected, but a carrier cousin is unaffected cousin. Functional studies using COS7 cells (fibroblast like) show that the variant reduces glutamate uptake compared to wild type protein.
PMID: 25497598 - Pyle et al 2015 - report a 30 yo male who presented with speech disturbance, dexterity problems and a deteriorating gait. His mother and cousin are also affected. The two cousins were found to have a heterozygous variant in SLC1A3 c.1361G>A:p.Arg454Gln. The disorder was not described as episodic.Created: 9 Jun 2021, 2:51 p.m. | Last Modified: 9 Jun 2021, 2:51 p.m.
Panel Version: 1.26
Phenotypes
Episodic ataxia, type 6, OMIM:612656; episodic ataxia type 6, MONDO:0012982
Publications
This is a brain channelopathy.Created: 20 Aug 2020, 8:53 a.m. | Last Modified: 20 Aug 2020, 8:53 a.m.
Panel Version: 1.4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Episodic ataxia, type 6, MIM# 612656
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Episodic ataxia, type 6, 612656
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_21_rating was removed from gene: SLC1A3. Tag Q2_21_phenotype was removed from gene: SLC1A3. Tag Q2_21_expert_review was removed from gene: SLC1A3.
Source Expert Review Red was added to SLC1A3. Rating Changed from Green List (high evidence) to Red List (low evidence)
Tag Q2_21_rating tag was added to gene: SLC1A3. Tag Q2_21_expert_review tag was added to gene: SLC1A3.
Tag Q2_21_rating was removed from gene: SLC1A3.
Gene: slc1a3 has been classified as Green List (High Evidence).
Phenotypes for gene: SLC1A3 were changed from Episodic ataxia, type 6, 612656 to Episodic ataxia, type 6, OMIM:612656; episodic ataxia type 6, MONDO:0012982
Publications for gene: SLC1A3 were set to 19139306
Tag Q2_21_phenotype tag was added to gene: SLC1A3.
Tag Q2_21_rating tag was added to gene: SLC1A3.
Publications for gene SLC1A3 were changed from to 19139306
Source NHS GMS was added to SLC1A3.
Mode of inheritance for gene SLC1A3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Episodic ataxia, type 6, 612656 for gene: SLC1A3
Source Expert Review Green was added to SLC1A3. Rating Changed from Red List (low evidence) to Green List (high evidence)
gene: SLC1A3 was added gene: SLC1A3 was added to Myotonia congenita. Sources: London North GLH Mode of inheritance for gene: SLC1A3 was set to