PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine

Robin Cloarec, Nadine Bruneau, Gabrielle Rudolf, Annick Massacrier, Manal Salmi, Marc Bataillard, Clotilde Boulay, Roberto Caraballo, Natalio Fejerman, Pierre Genton, Edouard Hirsch, Alasdair Hunter, Gaetan Lesca, Jacques Motte, Agathe Roubertie, Damien Sanlaville, Sau Wei Wong, Ying Hui Fu, Jacques Rochette, Louis J. PtáčekPierre Szepetowski

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Objective: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. Methods: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. Results: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in z50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. Conclusions: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations.

Original languageEnglish
Pages (from-to)2097-2103
Number of pages7
JournalNeurology
Volume79
Issue number21
DOIs
Publication statusPublished - 20 Nov 2012

Fingerprint

Chorea
Migraine Disorders
Seizures
Mutation
Migraine without Aura
Migraine with Aura
Familial paroxysmal dystonia
Exons
Aura
Proline
Introns

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Cloarec, R., Bruneau, N., Rudolf, G., Massacrier, A., Salmi, M., Bataillard, M., ... Szepetowski, P. (2012). PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine. Neurology, 79(21), 2097-2103. https://doi.org/10.1212/WNL.0b013e3182752c46

PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine. / Cloarec, Robin; Bruneau, Nadine; Rudolf, Gabrielle; Massacrier, Annick; Salmi, Manal; Bataillard, Marc; Boulay, Clotilde; Caraballo, Roberto; Fejerman, Natalio; Genton, Pierre; Hirsch, Edouard; Hunter, Alasdair; Lesca, Gaetan; Motte, Jacques; Roubertie, Agathe; Sanlaville, Damien; Wong, Sau Wei; Fu, Ying Hui; Rochette, Jacques; Ptáček, Louis J.; Szepetowski, Pierre.

In: Neurology, Vol. 79, No. 21, 20.11.2012, p. 2097-2103.

Research output: Contribution to journalArticle

Cloarec, R, Bruneau, N, Rudolf, G, Massacrier, A, Salmi, M, Bataillard, M, Boulay, C, Caraballo, R, Fejerman, N, Genton, P, Hirsch, E, Hunter, A, Lesca, G, Motte, J, Roubertie, A, Sanlaville, D, Wong, SW, Fu, YH, Rochette, J, Ptáček, LJ & Szepetowski, P 2012, 'PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine', Neurology, vol. 79, no. 21, pp. 2097-2103. https://doi.org/10.1212/WNL.0b013e3182752c46
Cloarec R, Bruneau N, Rudolf G, Massacrier A, Salmi M, Bataillard M et al. PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine. Neurology. 2012 Nov 20;79(21):2097-2103. https://doi.org/10.1212/WNL.0b013e3182752c46
Cloarec, Robin ; Bruneau, Nadine ; Rudolf, Gabrielle ; Massacrier, Annick ; Salmi, Manal ; Bataillard, Marc ; Boulay, Clotilde ; Caraballo, Roberto ; Fejerman, Natalio ; Genton, Pierre ; Hirsch, Edouard ; Hunter, Alasdair ; Lesca, Gaetan ; Motte, Jacques ; Roubertie, Agathe ; Sanlaville, Damien ; Wong, Sau Wei ; Fu, Ying Hui ; Rochette, Jacques ; Ptáček, Louis J. ; Szepetowski, Pierre. / PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine. In: Neurology. 2012 ; Vol. 79, No. 21. pp. 2097-2103.
@article{83142d37b3e74c539c6bedef0b0fdef7,
title = "PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine",
abstract = "Objective: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. Methods: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. Results: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in z50{\%} of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. Conclusions: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations.",
author = "Robin Cloarec and Nadine Bruneau and Gabrielle Rudolf and Annick Massacrier and Manal Salmi and Marc Bataillard and Clotilde Boulay and Roberto Caraballo and Natalio Fejerman and Pierre Genton and Edouard Hirsch and Alasdair Hunter and Gaetan Lesca and Jacques Motte and Agathe Roubertie and Damien Sanlaville and Wong, {Sau Wei} and Fu, {Ying Hui} and Jacques Rochette and Pt{\'a}ček, {Louis J.} and Pierre Szepetowski",
year = "2012",
month = "11",
day = "20",
doi = "10.1212/WNL.0b013e3182752c46",
language = "English",
volume = "79",
pages = "2097--2103",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "21",

}

TY - JOUR

T1 - PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine

AU - Cloarec, Robin

AU - Bruneau, Nadine

AU - Rudolf, Gabrielle

AU - Massacrier, Annick

AU - Salmi, Manal

AU - Bataillard, Marc

AU - Boulay, Clotilde

AU - Caraballo, Roberto

AU - Fejerman, Natalio

AU - Genton, Pierre

AU - Hirsch, Edouard

AU - Hunter, Alasdair

AU - Lesca, Gaetan

AU - Motte, Jacques

AU - Roubertie, Agathe

AU - Sanlaville, Damien

AU - Wong, Sau Wei

AU - Fu, Ying Hui

AU - Rochette, Jacques

AU - Ptáček, Louis J.

AU - Szepetowski, Pierre

PY - 2012/11/20

Y1 - 2012/11/20

N2 - Objective: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. Methods: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. Results: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in z50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. Conclusions: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations.

AB - Objective: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine. Methods: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate. Results: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in z50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. Conclusions: We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations.

UR - http://www.scopus.com/inward/record.url?scp=84868088726&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868088726&partnerID=8YFLogxK

U2 - 10.1212/WNL.0b013e3182752c46

DO - 10.1212/WNL.0b013e3182752c46

M3 - Article

C2 - 23077017

AN - SCOPUS:84868088726

VL - 79

SP - 2097

EP - 2103

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 21

ER -