The subject of this report is epilepsy, PRICKLE-related, which describes disease models of epilepsy using the Drosophila gene prickle (pk). There are 4 orthologous genes, designated PRICKLE1 to PRICKLE4, in humans. PRICKLE1 is implicated in a form of progressive myoclonic epilepsy (MIM:612437); there is some (not definitive) evidence that PRICKLE2 is also associated with epilepsy in humans (pubmed:21276947; pubmed:26942291). For the fly pk gene, classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. There is a second gene in flies, Dmel\esn, that is also orthologous to the human PRICKLE genes.
A UAS construct of a wild-type human Hsap\PRICKLE3 gene has been introduced into flies, but has not been characterized. None of the other human PRICKLE genes has been introduced into flies.
Amorphic and loss of function mutations of Dmel\pk have been classically described as exhibiting planar polarity defects in epithelium-derived structures. More recently, several alleles have been shown to produce seizure-sensitive phenotypes, including a lowered threshold to evoked electrophysiologically recorded seizure-like activity and "bang-sensitive" phenotypes. Physical and genetic interactions have been described for Dmel\pk; see below and in the gene report for pk.
[updated Sep. 2018 by FlyBase; FBrf0222196]
Epilepsy is a chronic neurological disease marked by recurrent unprovoked seizures. An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain, and may include sensory disturbance, loss of consciousness, or convulsions. [based on http://www.epilepsy.com/article/2014/4/revised-definition-epilepsy; Epilepsy Foundation; 2016.05.23]
Many to many: 4 human to 2 Drosophila; orthologous genes in human are PRICKLE1, PRICKLE2, PRICKLE3 and PRICKLE4.
High-scoring ortholog of human PRICKLE1 (reciprocal best hit), PRICKLE2, and PRICKLE3; lower scoring ortholog of PRICKLE4. Dmel\pk shares 32-36% identity and 44-49% similarity with the human genes.
