Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs: Associated with loss of function of Nav1.1

Wei Ping Liao, Yi Wu Shi, Yue Sheng Long, Yang Zeng, Tian Li, Mei Juan Yu, Tao Su, Ping Deng, Zhi Gang Lei, Shu Jun Xu, Wei Yi Deng, Xiao Rong Liu, Wei Wen Sun, Yong Hong Yi, Zao C. Xu, Shumin Duan

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Purpose: Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI) are associated with sodium channel α-subunit type-1 gene (SCN1A) mutations. Febrile seizures and partial seizures occur in both GEFS+ and SMEI; sporadic onset and seizure aggravation by antiepileptic drugs (AEDs) are features of SMEI. We thus searched gene mutations in isolated cases of partial epilepsy with antecedent FS (PEFS+) that showed seizure aggravations by AEDs. Methods: Genomic DNA from four patients was screened for mutations in SCN1A, SCN2A, SCN1B, and GABRG2 using denaturing high-performance liquid chromatography (dHPLC) and sequencing. Whole-cell patch clamp analysis was used to characterize biophysical properties of two newly defined mutants of Nav1.1 in tsA201 cells. Results: Two heterozygous de novo mutations of SCN1A (R946H and F1765L) were detected, which were proven to cause loss of function of Nav1.1. When the functional defects of mutants reported previously are compared, it is found that all mutants from PEFS+ have features of loss of function, whereas GEFS+ shows mild dysfunction excluding loss of function, coincident with mild clinical manifestations. PEFS+ is similar to SMEI clinically with possible AED-induced seizure aggravation and biophysiologically with features of loss of function, and different from SMEI by missense mutation without changes in hydrophobicity or polarity of the residues. Conclusions: Isolated milder PEFS+ may associate with SCN1A mutations and loss of function of Nav1.1, which may be the basis of seizure aggravation by sodium channel-blocking AEDs. This study characterized phenotypes biologically, which may be helpful in understanding the pathophysiologic basis, and further in management of the disease.

Original languageEnglish
Pages (from-to)1669-1678
Number of pages10
JournalEpilepsia
Volume51
Issue number9
DOIs
StatePublished - 2010

Fingerprint

Myoclonic Epilepsy
Febrile Seizures
Partial Epilepsy
Anticonvulsants
Seizures
Mutation
Sodium Channels
Missense Mutation
Disease Management
Hydrophobic and Hydrophilic Interactions
Genes
High Pressure Liquid Chromatography
Phenotype
DNA

Keywords

  • Channelopathy
  • Febrile seizures
  • Partial epilepsy
  • SCN1A
  • Sodium channel

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs : Associated with loss of function of Nav1.1. / Liao, Wei Ping; Shi, Yi Wu; Long, Yue Sheng; Zeng, Yang; Li, Tian; Yu, Mei Juan; Su, Tao; Deng, Ping; Lei, Zhi Gang; Xu, Shu Jun; Deng, Wei Yi; Liu, Xiao Rong; Sun, Wei Wen; Yi, Yong Hong; Xu, Zao C.; Duan, Shumin.

In: Epilepsia, Vol. 51, No. 9, 2010, p. 1669-1678.

Research output: Contribution to journalArticle

Liao, WP, Shi, YW, Long, YS, Zeng, Y, Li, T, Yu, MJ, Su, T, Deng, P, Lei, ZG, Xu, SJ, Deng, WY, Liu, XR, Sun, WW, Yi, YH, Xu, ZC & Duan, S 2010, 'Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs: Associated with loss of function of Nav1.1', Epilepsia, vol. 51, no. 9, pp. 1669-1678. https://doi.org/10.1111/j.1528-1167.2010.02645.x
Liao, Wei Ping ; Shi, Yi Wu ; Long, Yue Sheng ; Zeng, Yang ; Li, Tian ; Yu, Mei Juan ; Su, Tao ; Deng, Ping ; Lei, Zhi Gang ; Xu, Shu Jun ; Deng, Wei Yi ; Liu, Xiao Rong ; Sun, Wei Wen ; Yi, Yong Hong ; Xu, Zao C. ; Duan, Shumin. / Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs : Associated with loss of function of Nav1.1. In: Epilepsia. 2010 ; Vol. 51, No. 9. pp. 1669-1678.
@article{3278ab32c95c4697976e95f0ce292891,
title = "Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs: Associated with loss of function of Nav1.1",
abstract = "Purpose: Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI) are associated with sodium channel α-subunit type-1 gene (SCN1A) mutations. Febrile seizures and partial seizures occur in both GEFS+ and SMEI; sporadic onset and seizure aggravation by antiepileptic drugs (AEDs) are features of SMEI. We thus searched gene mutations in isolated cases of partial epilepsy with antecedent FS (PEFS+) that showed seizure aggravations by AEDs. Methods: Genomic DNA from four patients was screened for mutations in SCN1A, SCN2A, SCN1B, and GABRG2 using denaturing high-performance liquid chromatography (dHPLC) and sequencing. Whole-cell patch clamp analysis was used to characterize biophysical properties of two newly defined mutants of Nav1.1 in tsA201 cells. Results: Two heterozygous de novo mutations of SCN1A (R946H and F1765L) were detected, which were proven to cause loss of function of Nav1.1. When the functional defects of mutants reported previously are compared, it is found that all mutants from PEFS+ have features of loss of function, whereas GEFS+ shows mild dysfunction excluding loss of function, coincident with mild clinical manifestations. PEFS+ is similar to SMEI clinically with possible AED-induced seizure aggravation and biophysiologically with features of loss of function, and different from SMEI by missense mutation without changes in hydrophobicity or polarity of the residues. Conclusions: Isolated milder PEFS+ may associate with SCN1A mutations and loss of function of Nav1.1, which may be the basis of seizure aggravation by sodium channel-blocking AEDs. This study characterized phenotypes biologically, which may be helpful in understanding the pathophysiologic basis, and further in management of the disease.",
keywords = "Channelopathy, Febrile seizures, Partial epilepsy, SCN1A, Sodium channel",
author = "Liao, {Wei Ping} and Shi, {Yi Wu} and Long, {Yue Sheng} and Yang Zeng and Tian Li and Yu, {Mei Juan} and Tao Su and Ping Deng and Lei, {Zhi Gang} and Xu, {Shu Jun} and Deng, {Wei Yi} and Liu, {Xiao Rong} and Sun, {Wei Wen} and Yi, {Yong Hong} and Xu, {Zao C.} and Shumin Duan",
year = "2010",
doi = "10.1111/j.1528-1167.2010.02645.x",
language = "English",
volume = "51",
pages = "1669--1678",
journal = "Epilepsia",
issn = "0013-9580",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs

T2 - Associated with loss of function of Nav1.1

AU - Liao, Wei Ping

AU - Shi, Yi Wu

AU - Long, Yue Sheng

AU - Zeng, Yang

AU - Li, Tian

AU - Yu, Mei Juan

AU - Su, Tao

AU - Deng, Ping

AU - Lei, Zhi Gang

AU - Xu, Shu Jun

AU - Deng, Wei Yi

AU - Liu, Xiao Rong

AU - Sun, Wei Wen

AU - Yi, Yong Hong

AU - Xu, Zao C.

AU - Duan, Shumin

PY - 2010

Y1 - 2010

N2 - Purpose: Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI) are associated with sodium channel α-subunit type-1 gene (SCN1A) mutations. Febrile seizures and partial seizures occur in both GEFS+ and SMEI; sporadic onset and seizure aggravation by antiepileptic drugs (AEDs) are features of SMEI. We thus searched gene mutations in isolated cases of partial epilepsy with antecedent FS (PEFS+) that showed seizure aggravations by AEDs. Methods: Genomic DNA from four patients was screened for mutations in SCN1A, SCN2A, SCN1B, and GABRG2 using denaturing high-performance liquid chromatography (dHPLC) and sequencing. Whole-cell patch clamp analysis was used to characterize biophysical properties of two newly defined mutants of Nav1.1 in tsA201 cells. Results: Two heterozygous de novo mutations of SCN1A (R946H and F1765L) were detected, which were proven to cause loss of function of Nav1.1. When the functional defects of mutants reported previously are compared, it is found that all mutants from PEFS+ have features of loss of function, whereas GEFS+ shows mild dysfunction excluding loss of function, coincident with mild clinical manifestations. PEFS+ is similar to SMEI clinically with possible AED-induced seizure aggravation and biophysiologically with features of loss of function, and different from SMEI by missense mutation without changes in hydrophobicity or polarity of the residues. Conclusions: Isolated milder PEFS+ may associate with SCN1A mutations and loss of function of Nav1.1, which may be the basis of seizure aggravation by sodium channel-blocking AEDs. This study characterized phenotypes biologically, which may be helpful in understanding the pathophysiologic basis, and further in management of the disease.

AB - Purpose: Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI) are associated with sodium channel α-subunit type-1 gene (SCN1A) mutations. Febrile seizures and partial seizures occur in both GEFS+ and SMEI; sporadic onset and seizure aggravation by antiepileptic drugs (AEDs) are features of SMEI. We thus searched gene mutations in isolated cases of partial epilepsy with antecedent FS (PEFS+) that showed seizure aggravations by AEDs. Methods: Genomic DNA from four patients was screened for mutations in SCN1A, SCN2A, SCN1B, and GABRG2 using denaturing high-performance liquid chromatography (dHPLC) and sequencing. Whole-cell patch clamp analysis was used to characterize biophysical properties of two newly defined mutants of Nav1.1 in tsA201 cells. Results: Two heterozygous de novo mutations of SCN1A (R946H and F1765L) were detected, which were proven to cause loss of function of Nav1.1. When the functional defects of mutants reported previously are compared, it is found that all mutants from PEFS+ have features of loss of function, whereas GEFS+ shows mild dysfunction excluding loss of function, coincident with mild clinical manifestations. PEFS+ is similar to SMEI clinically with possible AED-induced seizure aggravation and biophysiologically with features of loss of function, and different from SMEI by missense mutation without changes in hydrophobicity or polarity of the residues. Conclusions: Isolated milder PEFS+ may associate with SCN1A mutations and loss of function of Nav1.1, which may be the basis of seizure aggravation by sodium channel-blocking AEDs. This study characterized phenotypes biologically, which may be helpful in understanding the pathophysiologic basis, and further in management of the disease.

KW - Channelopathy

KW - Febrile seizures

KW - Partial epilepsy

KW - SCN1A

KW - Sodium channel

UR - http://www.scopus.com/inward/record.url?scp=77955984540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955984540&partnerID=8YFLogxK

U2 - 10.1111/j.1528-1167.2010.02645.x

DO - 10.1111/j.1528-1167.2010.02645.x

M3 - Article

C2 - 20550552

AN - SCOPUS:77955984540

VL - 51

SP - 1669

EP - 1678

JO - Epilepsia

JF - Epilepsia

SN - 0013-9580

IS - 9

ER -