Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities

Carla Marini, Davide Mei, Teresa Temudo, Anna Rita Ferrari, Daniela Buti, Charlotte Dravet, Ana I. Dias, Eulalia Calado, Stefano Seri, Brian Neville, Juan Narbona, Evan Reid, Roberto Michelucci, Federico Sicca, Helen J. Cross, Renzo Guerrini*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Purpose: SCN1A is the most clinically relevant epilepsy gene, most mutations lead to severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). We studied 132 patients with epilepsy syndromes with seizures precipitated by fever, and performed phenotype-genotype correlations with SCN1A alterations. Methods: We included patients with SMEI including borderline SMEI (SMEB), GEFS+, febrile seizures (FS), or other seizure types precipitated by fever. We performed a clinical and genetic study focusing on SCN1A, using dHPLC, gene sequencing, and MLPA to detect genomic deletions/duplications on SMEI/SMEB patients. Results: We classified patients as: SMEI/SMEB = 55; GEFS+ = 26; and other phenotypes = 51. SCN1A analysis by dHPLC/sequencing revealed 40 mutations in 37 SMEI/SMEB (67%) and 3 GEFS+ (11.5%) probands. MLPA showed genomic deletions in 2 of 18 SMEI/SMEB. Most mutations were de novo (82%). SMEB patients carrying mutations (8) were more likely to have missense mutations (62.5%), conversely SMEI patients (31) had more truncating, splice site or genomic alterations (64.5%). SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS compared to those with missense mutations and without mutations (p = 0.00007, ANOVA test). None of the remaining patients with seizures precipitated by fever carried SCN1A mutations. Conclusion: We obtained a frequency of 71% SCN1A abnormalities in SMEI/SMEB and of 11.5% in GEFS+ probands. MLPA complements DNA sequencing of SCN1A increasing the mutation detection rate. SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS. This study confirms the high sensitivity of SCN1A for SMEI/SMEB phenotypes. © 2007 International League Against Epilepsy.

Original languageEnglish
Pages (from-to)1678-1685
Number of pages8
JournalEpilepsia
Volume48
Issue number9
Early online date11 Jun 2007
DOIs
Publication statusPublished - Sep 2007

Fingerprint

Myoclonic Epilepsy
Febrile Seizures
Epilepsy
Mutation
Missense Mutation
Age of Onset
Phenotype
Genetic Association Studies
Mutation Rate
DNA Sequence Analysis
Genes
Analysis of Variance

Keywords

  • fever-provoked seizures
  • GEFS+
  • MLPA
  • SCN1A
  • SMEI

Cite this

Marini, C., Mei, D., Temudo, T., Ferrari, A. R., Buti, D., Dravet, C., ... Guerrini, R. (2007). Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities. Epilepsia, 48(9), 1678-1685. https://doi.org/10.1111/j.1528-1167.2007.01122.x
Marini, Carla ; Mei, Davide ; Temudo, Teresa ; Ferrari, Anna Rita ; Buti, Daniela ; Dravet, Charlotte ; Dias, Ana I. ; Calado, Eulalia ; Seri, Stefano ; Neville, Brian ; Narbona, Juan ; Reid, Evan ; Michelucci, Roberto ; Sicca, Federico ; Cross, Helen J. ; Guerrini, Renzo. / Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities. In: Epilepsia. 2007 ; Vol. 48, No. 9. pp. 1678-1685.
@article{946134c44f064884986c2b203f11e7f9,
title = "Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities",
abstract = "Purpose: SCN1A is the most clinically relevant epilepsy gene, most mutations lead to severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). We studied 132 patients with epilepsy syndromes with seizures precipitated by fever, and performed phenotype-genotype correlations with SCN1A alterations. Methods: We included patients with SMEI including borderline SMEI (SMEB), GEFS+, febrile seizures (FS), or other seizure types precipitated by fever. We performed a clinical and genetic study focusing on SCN1A, using dHPLC, gene sequencing, and MLPA to detect genomic deletions/duplications on SMEI/SMEB patients. Results: We classified patients as: SMEI/SMEB = 55; GEFS+ = 26; and other phenotypes = 51. SCN1A analysis by dHPLC/sequencing revealed 40 mutations in 37 SMEI/SMEB (67{\%}) and 3 GEFS+ (11.5{\%}) probands. MLPA showed genomic deletions in 2 of 18 SMEI/SMEB. Most mutations were de novo (82{\%}). SMEB patients carrying mutations (8) were more likely to have missense mutations (62.5{\%}), conversely SMEI patients (31) had more truncating, splice site or genomic alterations (64.5{\%}). SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS compared to those with missense mutations and without mutations (p = 0.00007, ANOVA test). None of the remaining patients with seizures precipitated by fever carried SCN1A mutations. Conclusion: We obtained a frequency of 71{\%} SCN1A abnormalities in SMEI/SMEB and of 11.5{\%} in GEFS+ probands. MLPA complements DNA sequencing of SCN1A increasing the mutation detection rate. SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS. This study confirms the high sensitivity of SCN1A for SMEI/SMEB phenotypes. {\circledC} 2007 International League Against Epilepsy.",
keywords = "fever-provoked seizures, GEFS+, MLPA, SCN1A, SMEI",
author = "Carla Marini and Davide Mei and Teresa Temudo and Ferrari, {Anna Rita} and Daniela Buti and Charlotte Dravet and Dias, {Ana I.} and Eulalia Calado and Stefano Seri and Brian Neville and Juan Narbona and Evan Reid and Roberto Michelucci and Federico Sicca and Cross, {Helen J.} and Renzo Guerrini",
year = "2007",
month = "9",
doi = "10.1111/j.1528-1167.2007.01122.x",
language = "English",
volume = "48",
pages = "1678--1685",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley",
number = "9",

}

Marini, C, Mei, D, Temudo, T, Ferrari, AR, Buti, D, Dravet, C, Dias, AI, Calado, E, Seri, S, Neville, B, Narbona, J, Reid, E, Michelucci, R, Sicca, F, Cross, HJ & Guerrini, R 2007, 'Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities', Epilepsia, vol. 48, no. 9, pp. 1678-1685. https://doi.org/10.1111/j.1528-1167.2007.01122.x

Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities. / Marini, Carla; Mei, Davide; Temudo, Teresa; Ferrari, Anna Rita; Buti, Daniela; Dravet, Charlotte; Dias, Ana I.; Calado, Eulalia; Seri, Stefano; Neville, Brian; Narbona, Juan; Reid, Evan; Michelucci, Roberto; Sicca, Federico; Cross, Helen J.; Guerrini, Renzo.

In: Epilepsia, Vol. 48, No. 9, 09.2007, p. 1678-1685.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities

AU - Marini, Carla

AU - Mei, Davide

AU - Temudo, Teresa

AU - Ferrari, Anna Rita

AU - Buti, Daniela

AU - Dravet, Charlotte

AU - Dias, Ana I.

AU - Calado, Eulalia

AU - Seri, Stefano

AU - Neville, Brian

AU - Narbona, Juan

AU - Reid, Evan

AU - Michelucci, Roberto

AU - Sicca, Federico

AU - Cross, Helen J.

AU - Guerrini, Renzo

PY - 2007/9

Y1 - 2007/9

N2 - Purpose: SCN1A is the most clinically relevant epilepsy gene, most mutations lead to severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). We studied 132 patients with epilepsy syndromes with seizures precipitated by fever, and performed phenotype-genotype correlations with SCN1A alterations. Methods: We included patients with SMEI including borderline SMEI (SMEB), GEFS+, febrile seizures (FS), or other seizure types precipitated by fever. We performed a clinical and genetic study focusing on SCN1A, using dHPLC, gene sequencing, and MLPA to detect genomic deletions/duplications on SMEI/SMEB patients. Results: We classified patients as: SMEI/SMEB = 55; GEFS+ = 26; and other phenotypes = 51. SCN1A analysis by dHPLC/sequencing revealed 40 mutations in 37 SMEI/SMEB (67%) and 3 GEFS+ (11.5%) probands. MLPA showed genomic deletions in 2 of 18 SMEI/SMEB. Most mutations were de novo (82%). SMEB patients carrying mutations (8) were more likely to have missense mutations (62.5%), conversely SMEI patients (31) had more truncating, splice site or genomic alterations (64.5%). SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS compared to those with missense mutations and without mutations (p = 0.00007, ANOVA test). None of the remaining patients with seizures precipitated by fever carried SCN1A mutations. Conclusion: We obtained a frequency of 71% SCN1A abnormalities in SMEI/SMEB and of 11.5% in GEFS+ probands. MLPA complements DNA sequencing of SCN1A increasing the mutation detection rate. SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS. This study confirms the high sensitivity of SCN1A for SMEI/SMEB phenotypes. © 2007 International League Against Epilepsy.

AB - Purpose: SCN1A is the most clinically relevant epilepsy gene, most mutations lead to severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). We studied 132 patients with epilepsy syndromes with seizures precipitated by fever, and performed phenotype-genotype correlations with SCN1A alterations. Methods: We included patients with SMEI including borderline SMEI (SMEB), GEFS+, febrile seizures (FS), or other seizure types precipitated by fever. We performed a clinical and genetic study focusing on SCN1A, using dHPLC, gene sequencing, and MLPA to detect genomic deletions/duplications on SMEI/SMEB patients. Results: We classified patients as: SMEI/SMEB = 55; GEFS+ = 26; and other phenotypes = 51. SCN1A analysis by dHPLC/sequencing revealed 40 mutations in 37 SMEI/SMEB (67%) and 3 GEFS+ (11.5%) probands. MLPA showed genomic deletions in 2 of 18 SMEI/SMEB. Most mutations were de novo (82%). SMEB patients carrying mutations (8) were more likely to have missense mutations (62.5%), conversely SMEI patients (31) had more truncating, splice site or genomic alterations (64.5%). SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS compared to those with missense mutations and without mutations (p = 0.00007, ANOVA test). None of the remaining patients with seizures precipitated by fever carried SCN1A mutations. Conclusion: We obtained a frequency of 71% SCN1A abnormalities in SMEI/SMEB and of 11.5% in GEFS+ probands. MLPA complements DNA sequencing of SCN1A increasing the mutation detection rate. SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS. This study confirms the high sensitivity of SCN1A for SMEI/SMEB phenotypes. © 2007 International League Against Epilepsy.

KW - fever-provoked seizures

KW - GEFS+

KW - MLPA

KW - SCN1A

KW - SMEI

UR - http://www.scopus.com/inward/record.url?scp=34548423773&partnerID=8YFLogxK

UR - http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2007.01122.x/abstract

U2 - 10.1111/j.1528-1167.2007.01122.x

DO - 10.1111/j.1528-1167.2007.01122.x

M3 - Article

C2 - 17561957

VL - 48

SP - 1678

EP - 1685

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 9

ER -

Marini C, Mei D, Temudo T, Ferrari AR, Buti D, Dravet C et al. Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities. Epilepsia. 2007 Sep;48(9):1678-1685. https://doi.org/10.1111/j.1528-1167.2007.01122.x