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 GurnettAzhar 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

Research output: Contribution to journalArticle

133 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)572-581
Number of pages10
JournalAmerican Journal of Human Genetics
Volume83
Issue number5
DOIs
Publication statusPublished - 17 Nov 2008

Fingerprint

Progressive Myoclonic Epilepsy
Seizures
Ataxia
Pedigree
Mutation
Epilepsy
LIM Domain Proteins
Lightning
Chromosome Mapping
Zebrafish
Dementia
Brain
Hunt's syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Bassuk, A. G., Wallace, R. H., Buhr, A., Buller, A. R., Afawi, Z., Shimojo, M., ... 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. https://doi.org/10.1016/j.ajhg.2008.10.003

A Homozygous Mutation in Human PRICKLE1 Causes an Autosomal-Recessive Progressive Myoclonus Epilepsy-Ataxia Syndrome. / 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, Vol. 83, No. 5, 17.11.2008, p. 572-581.

Research output: Contribution to journalArticle

Bassuk, AG, Wallace, RH, Buhr, A, Buller, AR, Afawi, Z, Shimojo, M, Miyata, S, Chen, S, Gonzalez-Alegre, P, Griesbach, HL, Wu, S, Nashelsky, M, Vladar, EK, Antic, D, Ferguson, PJ, Cirak, S, Voit, T, Scott, MP, Axelrod, JD, Gurnett, C, Daoud, AS, Kivity, S, Neufeld, MY, Mazarib, A, Straussberg, R, Walid, S, Korczyn, AD, Slusarski, DC, Berkovic, SF & El-Shanti, HI 2008, 'A Homozygous Mutation in Human PRICKLE1 Causes an Autosomal-Recessive Progressive Myoclonus Epilepsy-Ataxia Syndrome', American Journal of Human Genetics, vol. 83, no. 5, pp. 572-581. https://doi.org/10.1016/j.ajhg.2008.10.003
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. / A Homozygous Mutation in Human PRICKLE1 Causes an Autosomal-Recessive Progressive Myoclonus Epilepsy-Ataxia Syndrome. In: American Journal of Human Genetics. 2008 ; Vol. 83, No. 5. pp. 572-581.
@article{86bd11612b3d403c835faa9cd03d5a8f,
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.",
author = "Bassuk, {Alexander G.} and Wallace, {Robyn H.} and Aimee Buhr and Buller, {Andrew R.} and Zaid Afawi and Masahito Shimojo and Shingo Miyata and Shan Chen and Pedro Gonzalez-Alegre and Griesbach, {Hilary L.} and Shu Wu and Marcus Nashelsky and Vladar, {Eszter K.} and Dragana Antic and Ferguson, {Polly J.} and Sebahattin Cirak and Thomas Voit and Scott, {Matthew P.} and Axelrod, {Jeffrey D.} and Christina Gurnett and Daoud, {Azhar S.} and Sara Kivity and Neufeld, {Miriam Y.} and Aziz Mazarib and Rachel Straussberg and Simri Walid and Korczyn, {Amos D.} and Slusarski, {Diane C.} and Berkovic, {Samuel F.} and El-Shanti, {Hatem I.}",
year = "2008",
month = "11",
day = "17",
doi = "10.1016/j.ajhg.2008.10.003",
language = "English",
volume = "83",
pages = "572--581",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - A Homozygous Mutation in Human PRICKLE1 Causes an Autosomal-Recessive Progressive Myoclonus Epilepsy-Ataxia Syndrome

AU - Bassuk, Alexander G.

AU - Wallace, Robyn H.

AU - Buhr, Aimee

AU - Buller, Andrew R.

AU - Afawi, Zaid

AU - Shimojo, Masahito

AU - Miyata, Shingo

AU - Chen, Shan

AU - Gonzalez-Alegre, Pedro

AU - Griesbach, Hilary L.

AU - Wu, Shu

AU - Nashelsky, Marcus

AU - Vladar, Eszter K.

AU - Antic, Dragana

AU - Ferguson, Polly J.

AU - Cirak, Sebahattin

AU - Voit, Thomas

AU - Scott, Matthew P.

AU - Axelrod, Jeffrey D.

AU - Gurnett, Christina

AU - Daoud, Azhar S.

AU - Kivity, Sara

AU - Neufeld, Miriam Y.

AU - Mazarib, Aziz

AU - Straussberg, Rachel

AU - Walid, Simri

AU - Korczyn, Amos D.

AU - Slusarski, Diane C.

AU - Berkovic, Samuel F.

AU - El-Shanti, Hatem I.

PY - 2008/11/17

Y1 - 2008/11/17

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=55049083176&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55049083176&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2008.10.003

DO - 10.1016/j.ajhg.2008.10.003

M3 - Article

C2 - 18976727

AN - SCOPUS:55049083176

VL - 83

SP - 572

EP - 581

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 5

ER -