This report describes episodic ataxia, type 1 (EA1); EA1 exhibits autosomal dominant inheritance. The human gene implicated in this disease in KCNA1, which encodes a voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system. There are multiple related genes in human that correspond to a single orthologous gene in Drosophila, Sh : Sh is the only KCNA-type potassium channel in flies; it is orthologous to 8 genes in this family in human. Many genetic reagents have been generated for Dmel\Sh, including classical loss-of-function alleles, RNAi targeting constructs, alleles caused by insertional mutagenesis, overexpression constructs, and a CRISPR/Cas9-based TKO construct.
The human Hsap\KCNA1 gene has been introduced into flies and stocks are available. It has not been used in context of this disease model.
The Drosophila model makes use of the Sh5 allele; hemizygous Sh5 males exhibit an anesthesia-induced leg shaking phenotype and various neurological defects. The Sh5 mutational lesion is analogous to an EA1-implicated variant ( KCNA1:p.Phe331Ile ). The Sh5 mutation also corresponds to a similar change at the analogous position for KCNA2 that is implicated in a form of developmental and epileptic encephalopathy ( KCNA2:p.Phe333Leu ; ClinVar:575248). The Drosophila model has been used to assess the efficacy of a candidate therapeutic drug.
[updated Nov. 2023 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 1; EA1](https://omim.org/entry/160120)
[POTASSIUM CHANNEL, VOLTAGE-GATED, SHAKER-RELATED SUBFAMILY, MEMBER 1; KCNA1](https://omim.org/entry/176260)
Episodic ataxia type 1 (EA1) is a potassium channelopathy characterized by constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with loss of both motor coordination and balance. Onset is usually in childhood or early adolescence. [GeneReviews, NBK25442; 2023.10.31]
Symptoms include continuous muscle movement (myokymia) and periodic ataxia. [from MIM:160120; 2023.10.31]
Episodic ataxia-1 (EA1) is caused by heterozygous mutation in the potassium channel gene KCNA1. [from MIM:160120; 2023.10.31]
KCNA1 encodes a voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, and also in the kidney. The functional channel is a homotetramer. [GeneCards, KCNA1; 2023.10.31]
Many to one: multiple human genes to 1 Drosophila gene.
High-scoring ortholog of the human KCNA genes (1 Drosophila to 8 human).
