Investigation of GRIN2A in common epilepsy phenotypes

Dennis Lal; Sandra Steinbrücker; Julian Schubert; Thomas Sander; Felicitas Becker; Yvonne Weber; Holger Lerche; Holger Thiele; Roland Krause; Anna Elina Lehesjoki; Peter Nürnberg; Aarno Palotie; Bernd A. Neubauer; Hiltrud Muhle; Ulrich Stephani; Ingo Helbig; Albert J. Becker; Susanne Schoch; Jörg Hansen; Thomas Dorn; Christin Hohl; Nicole Lüscher; Sarah von Spiczak; Johannes R. Lemke; Fritz Zimprich; Martha Feucht; Arvid Suls; Sarah Weckhuysen; Lieve Claes; Liesbet Deprez; Katrien Smets; Tine Van Dyck; Tine Deconinck; Peter De Jonghe; Rikke S. Møller; Laura L. Klitten; Helle Hjalgrim; Kiel Campus; Philipp Ostertag; Hol ger Trucks; Christian E. Elger; Ailing A. Kleefuß-Lie; Wolfram S. Kunz; Rainer Surges; Verena Gaus; Dieter Janz; Bettina Schmitz; Karl Martin Klein; Philipp S. Reif; Wolfgang H. Oertel; Hajo M. Hamer; Felix Rosenow; Claudia Kapser; Christoph J. Schankin; Bobby P C Koeleman; Carolien de Kovel; Dick Lindhout; Eva M. Reinthaler; Hannelore Steinboeck; Birgit Neo-phytou; Julia Geldner; Ursula Gruber-Sedlmayr; Edda Haberlandt; Gabriel M. Ronen; Janine Altmueller; Peter Nuernberg; Bernd Neubauer; Auli Sirén

doi:10.1016/j.eplepsyres.2015.05.010

Investigation of GRIN2A in common epilepsy phenotypes

Dennis Lal, Sandra Steinbrücker, Julian Schubert, Thomas Sander, Felicitas Becker, Yvonne Weber, Holger Lerche, Holger Thiele, Roland Krause, Anna Elina Lehesjoki, Peter Nürnberg, Aarno Palotie, Bernd A. Neubauer, Hiltrud Muhle, Ulrich Stephani, Ingo Helbig, Albert J. Becker, Susanne Schoch, Jörg Hansen, Thomas DornChristin Hohl, Nicole Lüscher, Sarah von Spiczak^*, Johannes R. Lemke, Fritz Zimprich, Martha Feucht, Arvid Suls, Sarah Weckhuysen, Lieve Claes, Liesbet Deprez, Katrien Smets, Tine Van Dyck, Tine Deconinck, Peter De Jonghe, Rikke S. Møller, Laura L. Klitten, Helle Hjalgrim, Kiel Campus, Philipp Ostertag, Hol ger Trucks, Christian E. Elger, Ailing A. Kleefuß-Lie, Wolfram S. Kunz, Rainer Surges, Verena Gaus, Dieter Janz, Bettina Schmitz, Karl Martin Klein, Philipp S. Reif, Wolfgang H. Oertel, Hajo M. Hamer, Felix Rosenow, Claudia Kapser, Christoph J. Schankin, Bobby P C Koeleman, Carolien de Kovel, Dick Lindhout, Eva M. Reinthaler, Hannelore Steinboeck, Birgit Neo-phytou, Julia Geldner, Ursula Gruber-Sedlmayr, Edda Haberlandt, Gabriel M. Ronen, Janine Altmueller, Peter Nuernberg, Bernd Neubauer, Auli Sirén

^*Corresponding author for this work

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

1 Citation (Scopus)

Abstract

Recently, mutations and deletions in the GRIN2A gene have been identified to predispose to benign and severe idiopathic focal epilepsies (IFE), revealing a higher incidence of GRIN2A alterations among the more severe phenotypes. This study aimed to explore the phenotypic boundaries of GRIN2A mutations by investigating patients with the two most common epilepsy syndromes: (i) idiopathic generalized epilepsy (IGE) and (ii) temporal lobe epilepsy (TLE). Whole exome sequencing data of 238 patients with IGE as well as Sanger sequencing of 84 patients with TLE were evaluated for GRIN2A sequence alterations. Two additional independent cohorts comprising 1469 IGE and 330 TLE patients were screened for structural deletions (>40. kb) involving GRIN2A. Apart from a presumably benign, non-segregating variant in a patient with juvenile absence epilepsy, neither mutations nor deletions were detected in either cohort. These findings suggest that mutations in GRIN2A preferentially are involved in genetic variance of pediatric IFE and do not contribute significantly to either adult focal epilepsies as TLE or generalized epilepsies.

Original language	English
Pages (from-to)	95-99
Number of pages	5
Journal	Epilepsy Research
Volume	115
DOIs	https://doi.org/10.1016/j.eplepsyres.2015.05.010
Publication status	Published - 1 Sept 2015

Keywords

Copy number variation
GRIN2A
Idiopathic generalized epilepsy
Mutation
Temporal lobe epilepsy

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10.1016/j.eplepsyres.2015.05.010

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Lal, D., Steinbrücker, S., Schubert, J., Sander, T., Becker, F., Weber, Y., Lerche, H., Thiele, H., Krause, R., Lehesjoki, A. E., Nürnberg, P., Palotie, A., Neubauer, B. A., Muhle, H., Stephani, U., Helbig, I., Becker, A. J., Schoch, S., Hansen, J., ... Sirén, A. (2015). Investigation of GRIN2A in common epilepsy phenotypes. Epilepsy Research, 115, 95-99. https://doi.org/10.1016/j.eplepsyres.2015.05.010

@article{b547d9c13b554f5ab3f0038d7e98c4eb,

title = "Investigation of GRIN2A in common epilepsy phenotypes",

abstract = "Recently, mutations and deletions in the GRIN2A gene have been identified to predispose to benign and severe idiopathic focal epilepsies (IFE), revealing a higher incidence of GRIN2A alterations among the more severe phenotypes. This study aimed to explore the phenotypic boundaries of GRIN2A mutations by investigating patients with the two most common epilepsy syndromes: (i) idiopathic generalized epilepsy (IGE) and (ii) temporal lobe epilepsy (TLE). Whole exome sequencing data of 238 patients with IGE as well as Sanger sequencing of 84 patients with TLE were evaluated for GRIN2A sequence alterations. Two additional independent cohorts comprising 1469 IGE and 330 TLE patients were screened for structural deletions (>40. kb) involving GRIN2A. Apart from a presumably benign, non-segregating variant in a patient with juvenile absence epilepsy, neither mutations nor deletions were detected in either cohort. These findings suggest that mutations in GRIN2A preferentially are involved in genetic variance of pediatric IFE and do not contribute significantly to either adult focal epilepsies as TLE or generalized epilepsies.",

keywords = "Copy number variation, GRIN2A, Idiopathic generalized epilepsy, Mutation, Temporal lobe epilepsy",

author = "Dennis Lal and Sandra Steinbr{\"u}cker and Julian Schubert and Thomas Sander and Felicitas Becker and Yvonne Weber and Holger Lerche and Holger Thiele and Roland Krause and Lehesjoki, {Anna Elina} and Peter N{\"u}rnberg and Aarno Palotie and Neubauer, {Bernd A.} and Hiltrud Muhle and Ulrich Stephani and Ingo Helbig and Becker, {Albert J.} and Susanne Schoch and J{\"o}rg Hansen and Thomas Dorn and Christin Hohl and Nicole L{\"u}scher and {von Spiczak}, Sarah and Lemke, {Johannes R.} and Fritz Zimprich and Martha Feucht and Arvid Suls and Sarah Weckhuysen and Lieve Claes and Liesbet Deprez and Katrien Smets and Dyck, {Tine Van} and Tine Deconinck and {De Jonghe}, Peter and M{\o}ller, {Rikke S.} and Klitten, {Laura L.} and Helle Hjalgrim and Kiel Campus and Philipp Ostertag and Trucks, {Hol ger} and Elger, {Christian E.} and Kleefu{\ss}-Lie, {Ailing A.} and Kunz, {Wolfram S.} and Rainer Surges and Verena Gaus and Dieter Janz and Bettina Schmitz and Klein, {Karl Martin} and Reif, {Philipp S.} and Oertel, {Wolfgang H.} and Hamer, {Hajo M.} and Felix Rosenow and Claudia Kapser and Schankin, {Christoph J.} and Koeleman, {Bobby P C} and {de Kovel}, Carolien and Dick Lindhout and Reinthaler, {Eva M.} and Hannelore Steinboeck and Birgit Neo-phytou and Julia Geldner and Ursula Gruber-Sedlmayr and Edda Haberlandt and Ronen, {Gabriel M.} and Janine Altmueller and Peter Nuernberg and Bernd Neubauer and Auli Sir{\'e}n",

year = "2015",

month = sep,

day = "1",

doi = "10.1016/j.eplepsyres.2015.05.010",

language = "English",

volume = "115",

pages = "95--99",

journal = "Epilepsy Research",

issn = "0920-1211",

publisher = "Elsevier",

}

Lal, D, Steinbrücker, S, Schubert, J, Sander, T, Becker, F, Weber, Y, Lerche, H, Thiele, H, Krause, R, Lehesjoki, AE, Nürnberg, P, Palotie, A, Neubauer, BA, Muhle, H, Stephani, U, Helbig, I, Becker, AJ, Schoch, S, Hansen, J, Dorn, T, Hohl, C, Lüscher, N, von Spiczak, S, Lemke, JR, Zimprich, F, Feucht, M, Suls, A, Weckhuysen, S, Claes, L, Deprez, L, Smets, K, Dyck, TV, Deconinck, T, De Jonghe, P, Møller, RS, Klitten, LL, Hjalgrim, H, Campus, K, Ostertag, P, Trucks, HG, Elger, CE, Kleefuß-Lie, AA, Kunz, WS, Surges, R, Gaus, V, Janz, D, Schmitz, B, Klein, KM, Reif, PS, Oertel, WH, Hamer, HM, Rosenow, F, Kapser, C, Schankin, CJ, Koeleman, BPC, de Kovel, C, Lindhout, D, Reinthaler, EM, Steinboeck, H, Neo-phytou, B, Geldner, J, Gruber-Sedlmayr, U, Haberlandt, E, Ronen, GM, Altmueller, J, Nuernberg, P, Neubauer, B & Sirén, A 2015, 'Investigation of GRIN2A in common epilepsy phenotypes', Epilepsy Research, vol. 115, pp. 95-99. https://doi.org/10.1016/j.eplepsyres.2015.05.010

TY - JOUR

T1 - Investigation of GRIN2A in common epilepsy phenotypes

AU - Lal, Dennis

AU - Steinbrücker, Sandra

AU - Schubert, Julian

AU - Sander, Thomas

AU - Becker, Felicitas

AU - Weber, Yvonne

AU - Lerche, Holger

AU - Thiele, Holger

AU - Krause, Roland

AU - Lehesjoki, Anna Elina

AU - Nürnberg, Peter

AU - Palotie, Aarno

AU - Neubauer, Bernd A.

AU - Muhle, Hiltrud

AU - Stephani, Ulrich

AU - Helbig, Ingo

AU - Becker, Albert J.

AU - Schoch, Susanne

AU - Hansen, Jörg

AU - Dorn, Thomas

AU - Hohl, Christin

AU - Lüscher, Nicole

AU - von Spiczak, Sarah

AU - Lemke, Johannes R.

AU - Zimprich, Fritz

AU - Feucht, Martha

AU - Suls, Arvid

AU - Weckhuysen, Sarah

AU - Claes, Lieve

AU - Deprez, Liesbet

AU - Smets, Katrien

AU - Dyck, Tine Van

AU - Deconinck, Tine

AU - De Jonghe, Peter

AU - Møller, Rikke S.

AU - Klitten, Laura L.

AU - Hjalgrim, Helle

AU - Campus, Kiel

AU - Ostertag, Philipp

AU - Trucks, Hol ger

AU - Elger, Christian E.

AU - Kleefuß-Lie, Ailing A.

AU - Kunz, Wolfram S.

AU - Surges, Rainer

AU - Gaus, Verena

AU - Janz, Dieter

AU - Schmitz, Bettina

AU - Klein, Karl Martin

AU - Reif, Philipp S.

AU - Oertel, Wolfgang H.

AU - Hamer, Hajo M.

AU - Rosenow, Felix

AU - Kapser, Claudia

AU - Schankin, Christoph J.

AU - Koeleman, Bobby P C

AU - de Kovel, Carolien

AU - Lindhout, Dick

AU - Reinthaler, Eva M.

AU - Steinboeck, Hannelore

AU - Neo-phytou, Birgit

AU - Geldner, Julia

AU - Gruber-Sedlmayr, Ursula

AU - Haberlandt, Edda

AU - Ronen, Gabriel M.

AU - Altmueller, Janine

AU - Nuernberg, Peter

AU - Neubauer, Bernd

AU - Sirén, Auli

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Recently, mutations and deletions in the GRIN2A gene have been identified to predispose to benign and severe idiopathic focal epilepsies (IFE), revealing a higher incidence of GRIN2A alterations among the more severe phenotypes. This study aimed to explore the phenotypic boundaries of GRIN2A mutations by investigating patients with the two most common epilepsy syndromes: (i) idiopathic generalized epilepsy (IGE) and (ii) temporal lobe epilepsy (TLE). Whole exome sequencing data of 238 patients with IGE as well as Sanger sequencing of 84 patients with TLE were evaluated for GRIN2A sequence alterations. Two additional independent cohorts comprising 1469 IGE and 330 TLE patients were screened for structural deletions (>40. kb) involving GRIN2A. Apart from a presumably benign, non-segregating variant in a patient with juvenile absence epilepsy, neither mutations nor deletions were detected in either cohort. These findings suggest that mutations in GRIN2A preferentially are involved in genetic variance of pediatric IFE and do not contribute significantly to either adult focal epilepsies as TLE or generalized epilepsies.

AB - Recently, mutations and deletions in the GRIN2A gene have been identified to predispose to benign and severe idiopathic focal epilepsies (IFE), revealing a higher incidence of GRIN2A alterations among the more severe phenotypes. This study aimed to explore the phenotypic boundaries of GRIN2A mutations by investigating patients with the two most common epilepsy syndromes: (i) idiopathic generalized epilepsy (IGE) and (ii) temporal lobe epilepsy (TLE). Whole exome sequencing data of 238 patients with IGE as well as Sanger sequencing of 84 patients with TLE were evaluated for GRIN2A sequence alterations. Two additional independent cohorts comprising 1469 IGE and 330 TLE patients were screened for structural deletions (>40. kb) involving GRIN2A. Apart from a presumably benign, non-segregating variant in a patient with juvenile absence epilepsy, neither mutations nor deletions were detected in either cohort. These findings suggest that mutations in GRIN2A preferentially are involved in genetic variance of pediatric IFE and do not contribute significantly to either adult focal epilepsies as TLE or generalized epilepsies.

KW - Copy number variation

KW - GRIN2A

KW - Idiopathic generalized epilepsy

KW - Mutation

KW - Temporal lobe epilepsy

UR - http://www.scopus.com/inward/record.url?scp=84955442963&partnerID=8YFLogxK

U2 - 10.1016/j.eplepsyres.2015.05.010

DO - 10.1016/j.eplepsyres.2015.05.010

M3 - Article

C2 - 26220384

AN - SCOPUS:84955442963

SN - 0920-1211

VL - 115

SP - 95

EP - 99

JO - Epilepsy Research

JF - Epilepsy Research

ER -

Investigation of GRIN2A in common epilepsy phenotypes

Abstract

Keywords

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