This report describes episodic ataxia, type 6 (EA6), which is a subtype of episodic ataxia; EA6 exhibits autosomal dominant inheritance. The human gene implicated in this disease is SLC1A3 (solute carrier family 1 member 3), which encodes a high-affinity glutamate transporter that functions in the termination of excitatory neurotransmission in central nervous system; it also functions as an anion channel. There are multiple genes in this family in both human and fly. The Drosophila gene most closely related to SLC1A3 is Eaat1, for which an amorphic mutation, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
UAS constructs of the human Hsap\SLC1A3 gene have been introduced into flies, including wild-type with different molecular tags and a disease-associated variant. Heterologous rescue (functional complementation) has been observed for the assayed larval locomotor defect.
Variant(s) implicated in human disease tested (as transgenic human gene, SLC1A3): the P290R variant form of the human gene (Hsap\SLC1A3PR.UAS.Venus) has been introduced into flies; the mechanism of this pathological variant has been studied in detail using the fly model. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): P243R in the fly Eaat1 gene (corresponds to P290R in the human SLC1A3 gene)(Eaat1PR.UAS.Venus).
Animals homozygous for an amorphic allele of Dmel\Eaat1 die during the larval stage; larvae exhibit locomotor and neurophysiology defects. Genetic interactions of Dmel\Eaat1 have been described; see the gene report for Dmel\Eaat1.
[updated Jun. 2017 by FlyBase; FBrf0222196]
Episodic ataxia is a neurologic condition characterized by spells of incoordination and imbalance, often associated with progressive ataxia (Jen et al., 2007; pubmed:17575281). [from MIM:160120; 2017.06.27]
[EPISODIC ATAXIA, TYPE 6; EA6](https://omim.org/entry/612656)
[SOLUTE CARRIER FAMILY 1 (GLIAL HIGH AFFINITY GLUTAMATE TRANSPORTER), MEMBER 3; SLC1A3](https://omim.org/entry/600111)
EA6 can also be associated with seizures, migraine, and hemiplegia (https://www.verywell.com/episodic-ataxia-2488684).
See general description above. EA6 is highly variable in severity and age of onset. [from MIM:612656; 2017.06.27]
Episodic ataxia type 6 (EA6) is caused by heterozygous mutation in the SLC1A3 gene. [from MIM:612656; 2017.06.27]
SLC1A3 functions in the termination of excitatory neurotransmission in central nervous system. [from Gene Cards, SLC1A3; 2017.06.27]
SLC1A3 (solute carrier family 1 member 3) is a member of a family of high-affinity sodium-dependent glutamate transporter molecules that regulate neurotransmitter concentrations at excitatory glutamatergic synapses (Kirschner et al., 1994; pubmed:8001975). SLC1A3 also functions as a glutamate-activated anion channel (summary by Winter et al., 2012; pubmed:23107647). [from MIM:600111; 2017.06.17]
Many to one (6 human to 1 Drosophila). Human genes include SLC1A3, SLC1A6, SLC1A5, SLC1A4, SLC1A1, SLC1A7. A related human gene, SLC1A2, is more closely related to Dmel\Eaat2.
High-scoring ortholog of SLC1A3 and SLC1A6; moderate-scoring ortholog of additional human genes (1 Drosophila to many human). Dmel\Eaat1 shares 44% identity and 63% similarity with SLC1A3 and SLC1A6.
