A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome

Alexander G Bassuk; Robyn H Wallace; Aimee Buhr; Andrew R Buller; Zaid Afawi; Masahito Shimojo; Shingo Miyata; Shan Chen; Pedro Gonzalez-Alegre; Hilary L Griesbach; Shu Wu; Marcus Nashelsky; Eszter K Vladar; Dragana Antic; Polly J Ferguson; Sebahattin Cirak; Thomas Voit; Matthew P Scott; Jeffrey D Axelrod; Christina Gurnett; Azhar S Daoud; Sara Kivity; Miriam Y Neufeld; Aziz Mazarib; Rachel Straussberg; Simri Walid; Amos D Korczyn; Diane C Slusarski; Samuel F Berkovic; Hatem I El-Shanti

doi:10.1016/j.ajhg.2008.10.003

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A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome

Journal article

Open access

Peer reviewed

A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome

Alexander G Bassuk, Robyn H Wallace, Aimee Buhr, Andrew R Buller, Zaid Afawi, Masahito Shimojo, Shingo Miyata, Shan Chen, Pedro Gonzalez-Alegre, Hilary L Griesbach, …

American journal of human genetics, Vol.83(5), pp.572-581

11/2008

DOI: 10.1016/j.ajhg.2008.10.003

PMCID: PMC2668041

PMID: 18976727

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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.

Genetic Markers

Mutation

Haplotypes

Amino Acid Sequence

LIM Domain Proteins

Physical Chromosome Mapping

Humans

Middle Aged

Molecular Sequence Data

Male

Genes, Recessive

Syndrome

Homozygote

Pedigree

Tumor Suppressor Proteins - genetics

Myoclonic Epilepsies, Progressive - genetics

Consanguinity

Chromosomes, Human, Pair 12

Ataxia - genetics

Microsatellite Repeats

Details

Title: Subtitle: A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy-ataxia syndrome
Creators: Alexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Robyn H Wallace - University of Queensland
Aimee Buhr
Andrew R Buller
Zaid Afawi
Masahito Shimojo
Shingo Miyata
Shan Chen
Pedro Gonzalez-Alegre
Hilary L Griesbach
Shu Wu
Marcus Nashelsky
Eszter K Vladar
Dragana Antic
Polly J Ferguson
Sebahattin Cirak
Thomas Voit
Matthew P Scott - Stanford University School of Medicine
Jeffrey D Axelrod
Christina Gurnett
Azhar S Daoud
Sara Kivity
Miriam Y Neufeld
Aziz Mazarib
Rachel Straussberg
Simri Walid
Amos D Korczyn
Diane C Slusarski
Samuel F Berkovic
Hatem I El-Shanti
Resource Type: Journal article
Publication Details: American journal of human genetics, Vol.83(5), pp.572-581
Publisher: United States
DOI: 10.1016/j.ajhg.2008.10.003
PMID: 18976727
PMCID: PMC2668041
ISSN: 0002-9297
eISSN: 1537-6605
Grant note: T32 CA009151 / NCI NIH HHS K01 MH067123 / NIMH NIH HHS P20RR020171 / NCRR NIH HHS MH067123 / NIMH NIH HHS Howard Hughes Medical Institute CA112369 / NCI NIH HHS K08 NS048174 / NINDS NIH HHS P20 RR020171 / NCRR NIH HHS K08 NS048174-05 / NINDS NIH HHS R01 CA112369 / NCI NIH HHS K08NS48174 / NINDS NIH HHS
Language: English
Date published: 11/2008
Academic Unit: Neurology; Stead Family Department of Pediatrics; Epidemiology; Pathology; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biology; Rheumatology, Allergy, and Immunology; Neurology (Pediatrics); Internal Medicine
Record Identifier: 9983992100202771

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