A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome by Bassuk Alexander G, Wallace Robyn H, Buhr Aimee, Buller Andrew R, Afawi Zaid, Shimojo Masahito, Miyata Shingo, Chen Shan, Gonzalez-Alegre Pedro, Griesbach Hilary L, Wu Shu, Nashelsky Marcus, Vladar Eszter K, Antic Dragana, Ferguson Polly J, Cirak Sebahattin, Voit Thomas, Scott Matthew P, Axelrod Jeffrey D, Gurnett Christina, Daoud Azhar S, Kivity Sara, Neufeld Miriam Y, Mazarib Aziz, Straussberg Rachel, Walid Simri, Korczyn Amos D, Slusarski Diane C, Berkovic Samuel F, El-Shanti Hatem I in American journal of human genetics (2008).

[PMID: 18976727] PubMed


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.

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