Open AccessA New, Progressive Myoclonic Epilepsy: Is It a Chronicle of the Noncanonical or a Failure to REST?
Author(s) -
Gallagher Martin
Publication year - 2009
Publication title -
epilepsy currents
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.415
H-Index - 22
eISSN - 1535-7511
pISSN - 1535-7597
DOI - 10.1111/j.1535-7511.2009.01300.x
Subject(s) - epilepsy , ataxia , progressive myoclonus epilepsy , myoclonus , hum , mutation , medicine , rest (music) , genetics , neuroscience , biology , gene , performance art , art history , art
Progressive myoclonus epilepsy (PME) is a syndrome characterized by myoclonic seizures (lightning‐like jerks), generalized convulsive seizures, and varying degrees of neurological decline, especially ataxia and dementia. Previously, we characterized three pedigrees of individuals with PME and ataxia, where either clinical features or linkage mapping excluded known PME loci. This report identifies a mutation in PRICKLE1 (also known as RILP for REST/NRSF interacting LIM domain protein) in all three of these pedigrees. The identified PRICKLE1 mutation blocks the PRICKLE1 and REST interaction in vitro and disrupts the normal function of PRICKLE1 in an in vivo zebrafish overexpression system. PRICKLE1 is expressed in brain regions implicated in epilepsy and ataxia in mice and humans, and, to our knowledge, is the first molecule in the noncanonical WNT signaling pathway to be directly implicated in human epilepsy.