Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

Hsien Yang Lee; Yong Huang; Nadine Bruneau; Patrice Roll; Elisha D.O. Roberson; Mark Hermann; Emily Quinn; James Maas; Robert Edwards; Tetsuo Ashizawa; Betul Baykan; Kailash Bhatia; Susan Bressman; Michiko K. Bruno; Ewout R. Brunt; Roberto Caraballo; Bernard Echenne; Natalio Fejerman; Steve Frucht; Christina A. Gurnett; Edouard Hirsch; Henry Houlden; Joseph Jankovic; Wei Ling Lee; David R. Lynch; Shehla Mohammed; Ulrich Müller; Mark P. Nespeca; David Renner; Jacques Rochette; Gabrielle Rudolf; Shinji Saiki; Bing Wen Soong; Kathryn J. Swoboda; Sam Tucker; Nicholas Wood; Michael Hanna; Anne M. Bowcock; Pierre Szepetowski; Ying Hui Fu; Louis J. Ptáček

doi:10.1016/j.celrep.2011.11.001

Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

Hsien Yang Lee, Yong Huang, Nadine Bruneau, Patrice Roll, Elisha D.O. Roberson, Mark Hermann, Emily Quinn, James Maas, Robert Edwards, Tetsuo Ashizawa, Betul Baykan, Kailash Bhatia, Susan Bressman, Michiko K. Bruno, Ewout R. Brunt, Roberto Caraballo, Bernard Echenne, Natalio Fejerman, Steve Frucht, Christina A. GurnettEdouard Hirsch, Henry Houlden, Joseph Jankovic, Wei Ling Lee, David R. Lynch, Shehla Mohammed, Ulrich Müller, Mark P. Nespeca, David Renner, Jacques Rochette, Gabrielle Rudolf, Shinji Saiki, Bing Wen Soong, Kathryn J. Swoboda, Sam Tucker, Nicholas Wood, Michael Hanna, Anne M. Bowcock, Pierre Szepetowski, Ying Hui Fu, Louis J. Ptáček

Icahn School of Medicine at Mount Sinai

Research output: Contribution to journal › Article › peer-review

240 Scopus citations

Abstract

Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

Original language	English
Pages (from-to)	2-12
Number of pages	11
Journal	Cell Reports
Volume	1
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2011.11.001
State	Published - 26 Jan 2012

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Lee, H. Y., Huang, Y., Bruneau, N., Roll, P., Roberson, E. D. O., Hermann, M., Quinn, E., Maas, J., Edwards, R., Ashizawa, T., Baykan, B., Bhatia, K., Bressman, S., Bruno, M. K., Brunt, E. R., Caraballo, R., Echenne, B., Fejerman, N., Frucht, S., ... Ptáček, L. J. (2012). Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions. Cell Reports, 1(1), 2-12. https://doi.org/10.1016/j.celrep.2011.11.001

@article{da97a182e93d4bb5968eec0494ee7998,

title = "Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions",

abstract = "Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.",

author = "Lee, {Hsien Yang} and Yong Huang and Nadine Bruneau and Patrice Roll and Roberson, {Elisha D.O.} and Mark Hermann and Emily Quinn and James Maas and Robert Edwards and Tetsuo Ashizawa and Betul Baykan and Kailash Bhatia and Susan Bressman and Bruno, {Michiko K.} and Brunt, {Ewout R.} and Roberto Caraballo and Bernard Echenne and Natalio Fejerman and Steve Frucht and Gurnett, {Christina A.} and Edouard Hirsch and Henry Houlden and Joseph Jankovic and Lee, {Wei Ling} and Lynch, {David R.} and Shehla Mohammed and Ulrich M{\"u}ller and Nespeca, {Mark P.} and David Renner and Jacques Rochette and Gabrielle Rudolf and Shinji Saiki and Soong, {Bing Wen} and Swoboda, {Kathryn J.} and Sam Tucker and Nicholas Wood and Michael Hanna and Bowcock, {Anne M.} and Pierre Szepetowski and Fu, {Ying Hui} and Pt{\'a}{\v c}ek, {Louis J.}",

note = "Funding Information: We thank Dr. Nicholas Lenn for patient referrals. We are grateful to all the families for their participation in this research. This work was supported by grants from the Dystonia Medical Research Foundation, the Bachmann-Strauss Dystonia Parkinson Foundation, NIH (grant NS043533 to L.P., grant U54 RR19481), the Sandler Neurogenetics Fund (Y.-H.F. and L.P.), ANR (grant EPILAND to P.S.), and INSERM. L.J.P. is an investigator of the Howard Hughes Medical Institute. ",

year = "2012",

month = jan,

day = "26",

doi = "10.1016/j.celrep.2011.11.001",

language = "English",

volume = "1",

pages = "2--12",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

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Lee, HY, Huang, Y, Bruneau, N, Roll, P, Roberson, EDO, Hermann, M, Quinn, E, Maas, J, Edwards, R, Ashizawa, T, Baykan, B, Bhatia, K, Bressman, S, Bruno, MK, Brunt, ER, Caraballo, R, Echenne, B, Fejerman, N, Frucht, S, Gurnett, CA, Hirsch, E, Houlden, H, Jankovic, J, Lee, WL, Lynch, DR, Mohammed, S, Müller, U, Nespeca, MP, Renner, D, Rochette, J, Rudolf, G, Saiki, S, Soong, BW, Swoboda, KJ, Tucker, S, Wood, N, Hanna, M, Bowcock, AM, Szepetowski, P, Fu, YH & Ptáček, LJ 2012, 'Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions', Cell Reports, vol. 1, no. 1, pp. 2-12. https://doi.org/10.1016/j.celrep.2011.11.001

TY - JOUR

T1 - Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

AU - Lee, Hsien Yang

AU - Huang, Yong

AU - Bruneau, Nadine

AU - Roll, Patrice

AU - Roberson, Elisha D.O.

AU - Hermann, Mark

AU - Quinn, Emily

AU - Maas, James

AU - Edwards, Robert

AU - Ashizawa, Tetsuo

AU - Baykan, Betul

AU - Bhatia, Kailash

AU - Bressman, Susan

AU - Bruno, Michiko K.

AU - Brunt, Ewout R.

AU - Caraballo, Roberto

AU - Echenne, Bernard

AU - Fejerman, Natalio

AU - Frucht, Steve

AU - Gurnett, Christina A.

AU - Hirsch, Edouard

AU - Houlden, Henry

AU - Jankovic, Joseph

AU - Lee, Wei Ling

AU - Lynch, David R.

AU - Mohammed, Shehla

AU - Müller, Ulrich

AU - Nespeca, Mark P.

AU - Renner, David

AU - Rochette, Jacques

AU - Rudolf, Gabrielle

AU - Saiki, Shinji

AU - Soong, Bing Wen

AU - Swoboda, Kathryn J.

AU - Tucker, Sam

AU - Wood, Nicholas

AU - Hanna, Michael

AU - Bowcock, Anne M.

AU - Szepetowski, Pierre

AU - Fu, Ying Hui

AU - Ptáček, Louis J.

N1 - Funding Information: We thank Dr. Nicholas Lenn for patient referrals. We are grateful to all the families for their participation in this research. This work was supported by grants from the Dystonia Medical Research Foundation, the Bachmann-Strauss Dystonia Parkinson Foundation, NIH (grant NS043533 to L.P., grant U54 RR19481), the Sandler Neurogenetics Fund (Y.-H.F. and L.P.), ANR (grant EPILAND to P.S.), and INSERM. L.J.P. is an investigator of the Howard Hughes Medical Institute.

PY - 2012/1/26

Y1 - 2012/1/26

N2 - Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

AB - Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

UR - http://www.scopus.com/inward/record.url?scp=84856144700&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2011.11.001

DO - 10.1016/j.celrep.2011.11.001

M3 - Article

C2 - 22832103

AN - SCOPUS:84856144700

SN - 2211-1247

VL - 1

SP - 2

EP - 12

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -

Mutations in the Gene PRRT2 Cause Paroxysmal Kinesigenic Dyskinesia with Infantile Convulsions

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