title: A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Bassuk
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Wallace
authors.forename: Aimee
authors.initials: A
authors.lastname: Buhr
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Buller
authors.forename: Zaid
authors.initials: Z
authors.lastname: Afawi
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimojo
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyata
authors.forename: Shan
authors.initials: S
authors.lastname: Chen
authors.forename: Pedro
authors.initials: P
authors.lastname: Gonzalez-Alegre
authors.forename: Hilary L
authors.initials: HL
authors.lastname: Griesbach
authors.forename: Shu
authors.initials: S
authors.lastname: Wu
authors.forename: Marcus
authors.initials: M
authors.lastname: Nashelsky
authors.forename: Eszter K
authors.initials: EK
authors.lastname: Vladar
authors.forename: Dragana
authors.initials: D
authors.lastname: Antic
authors.forename: Polly J
authors.initials: PJ
authors.lastname: Ferguson
authors.forename: Sebahattin
authors.initials: S
authors.lastname: Cirak
authors.forename: Thomas
authors.initials: T
authors.lastname: Voit
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Scott
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Axelrod
authors.forename: Christina
authors.initials: C
authors.lastname: Gurnett
authors.forename: Azhar S
authors.initials: AS
authors.lastname: Daoud
authors.forename: Sara
authors.initials: S
authors.lastname: Kivity
authors.forename: Miriam Y
authors.initials: MY
authors.lastname: Neufeld
authors.forename: Aziz
authors.initials: A
authors.lastname: Mazarib
authors.forename: Rachel
authors.initials: R
authors.lastname: Straussberg
authors.forename: Simri
authors.initials: S
authors.lastname: Walid
authors.forename: Amos D
authors.initials: AD
authors.lastname: Korczyn
authors.forename: Diane C
authors.initials: DC
authors.lastname: Slusarski
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Hatem I
authors.initials: HI
authors.lastname: El-Shanti
mesh_terms: D000595:Amino Acid Sequence; D001259:Ataxia / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12; D003241:Consanguinity; D005808:Genes, Recessive; D005819:Genetic Markers; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D060588:LIM Domain Proteins; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020191:Myoclonic Epilepsies, Progressive / Q000235:genetics*; D010375:Pedigree; D020161:Physical Chromosome Mapping; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D060588:LIM Domain Proteins; C515173:PRICKLE1 protein, human; D025521:Tumor Suppressor Proteins