Skeletal muscle channelopathy

Gene: SLC1A3

Red List (low evidence)

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

Red List (low evidence)

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

• 16116111
• 19139306
• 25497598

Red List (low evidence)

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

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Episodic ataxia, type 6, 612656

Publications

• de Vries et al 2009 Arch Neurol 66. 97-101 PMID: 19139306

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