Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

Markus Wolff, Katrine M Johannesen, Ulrike B S Hedrich, Silvia Masnada, Guido Rubboli, Elena Gardella, Gaetan Lesca, Dorothée Ville, Mathieu Milh, Laurent Villard, Alexandra Afenjar, Sandra Chantot-Bastaraud, Cyril Mignot, Caroline Lardennois, Caroline Nava, Niklas Schwarz, Marion Gérard, Laurence Perrin, Diane Doummar, Stéphane AuvinMaria J Miranda, Maja Hempel, Eva Brilstra, Nine Knoers, Nienke Verbeek, Marjan van Kempen, Kees P Braun, Grazia Mancini, Saskia Biskup, Konstanze Hörtnagel, Miriam Döcker, Thomas Bast, Tobias Loddenkemper, Lily Wong-Kisiel, Friedrich M Baumeister, Walid Fazeli, Pasquale Striano, Robertino Dilena, Elena Fontana, Federico Zara, Gerhard Kurlemann, Joerg Klepper, Jess G Thoene, Daniel H Arndt, Nicolas Deconinck, Thomas Schmitt-Mechelke, Oliver Maier, Hiltrud Muhle, Marina Trivisano, Nicola Specchio

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (
Original languageEnglish
Pages (from-to)1316-1336
Number of pages21
JournalBrain
Volume140
Issue number5
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Genetic Heterogeneity
NAV1.2 Voltage-Gated Sodium Channel
Epilepsy
Brain Diseases
Phenotype
Mutation
Therapeutics
Genes
Neurodevelopmental Disorders

Keywords

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Child, Preschool
  • Denmark
  • Epilepsy
  • Female
  • Humans
  • Infant
  • Male
  • Mutation
  • NAV1.2 Voltage-Gated Sodium Channel
  • Neurodevelopmental Disorders
  • Phenotype
  • Sodium Channel Blockers
  • Young Adult
  • Journal Article

Cite this

Wolff, M., Johannesen, K. M., Hedrich, U. B. S., Masnada, S., Rubboli, G., Gardella, E., ... Specchio, N. (2017). Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain, 140(5), 1316-1336. https://doi.org/10.1093/brain/awx054

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. / Wolff, Markus; Johannesen, Katrine M; Hedrich, Ulrike B S; Masnada, Silvia; Rubboli, Guido; Gardella, Elena; Lesca, Gaetan; Ville, Dorothée; Milh, Mathieu; Villard, Laurent; Afenjar, Alexandra; Chantot-Bastaraud, Sandra; Mignot, Cyril; Lardennois, Caroline; Nava, Caroline; Schwarz, Niklas; Gérard, Marion; Perrin, Laurence; Doummar, Diane; Auvin, Stéphane; Miranda, Maria J; Hempel, Maja; Brilstra, Eva; Knoers, Nine; Verbeek, Nienke; van Kempen, Marjan; Braun, Kees P; Mancini, Grazia; Biskup, Saskia; Hörtnagel, Konstanze; Döcker, Miriam; Bast, Thomas; Loddenkemper, Tobias; Wong-Kisiel, Lily; Baumeister, Friedrich M; Fazeli, Walid; Striano, Pasquale; Dilena, Robertino; Fontana, Elena; Zara, Federico; Kurlemann, Gerhard; Klepper, Joerg; Thoene, Jess G; Arndt, Daniel H; Deconinck, Nicolas; Schmitt-Mechelke, Thomas; Maier, Oliver; Muhle, Hiltrud; Trivisano, Marina; Specchio, Nicola.

In: Brain, Vol. 140, No. 5, 01.05.2017, p. 1316-1336.

Research output: Contribution to journalArticle

Wolff, M, Johannesen, KM, Hedrich, UBS, Masnada, S, Rubboli, G, Gardella, E, Lesca, G, Ville, D, Milh, M, Villard, L, Afenjar, A, Chantot-Bastaraud, S, Mignot, C, Lardennois, C, Nava, C, Schwarz, N, Gérard, M, Perrin, L, Doummar, D, Auvin, S, Miranda, MJ, Hempel, M, Brilstra, E, Knoers, N, Verbeek, N, van Kempen, M, Braun, KP, Mancini, G, Biskup, S, Hörtnagel, K, Döcker, M, Bast, T, Loddenkemper, T, Wong-Kisiel, L, Baumeister, FM, Fazeli, W, Striano, P, Dilena, R, Fontana, E, Zara, F, Kurlemann, G, Klepper, J, Thoene, JG, Arndt, DH, Deconinck, N, Schmitt-Mechelke, T, Maier, O, Muhle, H, Trivisano, M & Specchio, N 2017, 'Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders', Brain, vol. 140, no. 5, pp. 1316-1336. https://doi.org/10.1093/brain/awx054
Wolff M, Johannesen KM, Hedrich UBS, Masnada S, Rubboli G, Gardella E et al. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain. 2017 May 1;140(5):1316-1336. https://doi.org/10.1093/brain/awx054
Wolff, Markus ; Johannesen, Katrine M ; Hedrich, Ulrike B S ; Masnada, Silvia ; Rubboli, Guido ; Gardella, Elena ; Lesca, Gaetan ; Ville, Dorothée ; Milh, Mathieu ; Villard, Laurent ; Afenjar, Alexandra ; Chantot-Bastaraud, Sandra ; Mignot, Cyril ; Lardennois, Caroline ; Nava, Caroline ; Schwarz, Niklas ; Gérard, Marion ; Perrin, Laurence ; Doummar, Diane ; Auvin, Stéphane ; Miranda, Maria J ; Hempel, Maja ; Brilstra, Eva ; Knoers, Nine ; Verbeek, Nienke ; van Kempen, Marjan ; Braun, Kees P ; Mancini, Grazia ; Biskup, Saskia ; Hörtnagel, Konstanze ; Döcker, Miriam ; Bast, Thomas ; Loddenkemper, Tobias ; Wong-Kisiel, Lily ; Baumeister, Friedrich M ; Fazeli, Walid ; Striano, Pasquale ; Dilena, Robertino ; Fontana, Elena ; Zara, Federico ; Kurlemann, Gerhard ; Klepper, Joerg ; Thoene, Jess G ; Arndt, Daniel H ; Deconinck, Nicolas ; Schmitt-Mechelke, Thomas ; Maier, Oliver ; Muhle, Hiltrud ; Trivisano, Marina ; Specchio, Nicola. / Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. In: Brain. 2017 ; Vol. 140, No. 5. pp. 1316-1336.
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AU - Johannesen, Katrine M

AU - Hedrich, Ulrike B S

AU - Masnada, Silvia

AU - Rubboli, Guido

AU - Gardella, Elena

AU - Lesca, Gaetan

AU - Ville, Dorothée

AU - Milh, Mathieu

AU - Villard, Laurent

AU - Afenjar, Alexandra

AU - Chantot-Bastaraud, Sandra

AU - Mignot, Cyril

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AU - Nava, Caroline

AU - Schwarz, Niklas

AU - Gérard, Marion

AU - Perrin, Laurence

AU - Doummar, Diane

AU - Auvin, Stéphane

AU - Miranda, Maria J

AU - Hempel, Maja

AU - Brilstra, Eva

AU - Knoers, Nine

AU - Verbeek, Nienke

AU - van Kempen, Marjan

AU - Braun, Kees P

AU - Mancini, Grazia

AU - Biskup, Saskia

AU - Hörtnagel, Konstanze

AU - Döcker, Miriam

AU - Bast, Thomas

AU - Loddenkemper, Tobias

AU - Wong-Kisiel, Lily

AU - Baumeister, Friedrich M

AU - Fazeli, Walid

AU - Striano, Pasquale

AU - Dilena, Robertino

AU - Fontana, Elena

AU - Zara, Federico

AU - Kurlemann, Gerhard

AU - Klepper, Joerg

AU - Thoene, Jess G

AU - Arndt, Daniel H

AU - Deconinck, Nicolas

AU - Schmitt-Mechelke, Thomas

AU - Maier, Oliver

AU - Muhle, Hiltrud

AU - Trivisano, Marina

AU - Specchio, Nicola

N1 - © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2017/5/1

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N2 - Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (

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KW - Humans

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KW - Male

KW - Mutation

KW - NAV1.2 Voltage-Gated Sodium Channel

KW - Neurodevelopmental Disorders

KW - Phenotype

KW - Sodium Channel Blockers

KW - Young Adult

KW - Journal Article

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JF - Brain

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