PUBLICATION
A Homozygous Mutation in Human PRICKLE1 Causes an Autosomal-Recessive Progressive Myoclonus Epilepsy-Ataxia Syndrome
- Authors
- Bassuk, A.G., Wallace, R.H., Buhr, A., Buller, A.R., Afawi, Z., Shimojo, M., Miyata, S., Chen, S., Gonzalez-Alegre, P., Griesbach, H.L., Wu, S., Nashelsky, M., Vladar, E.K., Antic, D., Ferguson, P.J., Cirak, S., Voit, T., Scott, M.P., Axelrod, J.D., Gurnett, C., Daoud, A.S., Kivity, S., Neufeld, M.Y., Mazarib, A., Straussberg, R., Walid, S., Korczyn, A.D., Slusarski, D.C., Berkovic, S.F., and El-Shanti, H.I.
- ID
- ZDB-PUB-081105-6
- Date
- 2008
- Source
- American journal of human genetics 83(5): 572-581 (Journal)
- Registered Authors
- Slusarski, Diane C.
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Ataxia/genetics*
- Chromosomes, Human, Pair 12
- Consanguinity
- Genes, Recessive
- Genetic Markers
- Haplotypes
- Homozygote*
- Humans
- LIM Domain Proteins
- Male
- Microsatellite Repeats
- Middle Aged
- Molecular Sequence Data
- Mutation*
- Myoclonic Epilepsies, Progressive/genetics*
- Pedigree
- Physical Chromosome Mapping
- Syndrome
- Tumor Suppressor Proteins/genetics*
- PubMed
- 18976727 Full text @ Am. J. Hum. Genet.
Citation
Bassuk, A.G., Wallace, R.H., Buhr, A., Buller, A.R., Afawi, Z., Shimojo, M., Miyata, S., Chen, S., Gonzalez-Alegre, P., Griesbach, H.L., Wu, S., Nashelsky, M., Vladar, E.K., Antic, D., Ferguson, P.J., Cirak, S., Voit, T., Scott, M.P., Axelrod, J.D., Gurnett, C., Daoud, A.S., Kivity, S., Neufeld, M.Y., Mazarib, A., Straussberg, R., Walid, S., Korczyn, A.D., Slusarski, D.C., Berkovic, S.F., and El-Shanti, H.I. (2008) A Homozygous Mutation in Human PRICKLE1 Causes an Autosomal-Recessive Progressive Myoclonus Epilepsy-Ataxia Syndrome. American journal of human genetics. 83(5):572-581.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping