Variable epilepsy phenotypes associated with a familial intragenic deletion of the SCN1A gene

Renzo Guerrini, Elena Cellini, Davide Mei, Tiziana Metitieri, Cristina Petrelli, Daniela Pucatti, Carla Marini, Nelia Zamponi

Research output: Contribution to journalArticle

Abstract

Deletions and duplications/amplifications of the α1-sodium channel subunit (SCN1A) gene occur in about 12% of patients with Dravet syndrome (DS) who are otherwise mutation-negative. Such genomic abnormalities cause loss of function, with severe phenotypes, reproductive disadvantage and, therefore, sporadic occurrence. Inherited mutations, occurring in ∼5% of patients with DS, are usually missense; transmission occurs from a mildly affected parent exhibiting febrile seizures (FS) or the generalized epilepsy with febrile seizures plus (GEFS+) spectrum. We identified an intragenic SCN1A deletion in a three-generation, clinically heterogeneous family. Sequence analysis of SCN9A, a putative modifier, ruled out pathogenic mutations, variants, or putative disease-associated haplotype segregating with phenotype severity. Intrafamilial variability in phenotype severity indicates that SCN1A loss of function causes a phenotypic spectrum in which seizures precipitated by fever are prominent and schematic syndrome subdivisions would be inappropriate. SCN1A deletions should be ruled out even in individuals with mild phenotypes.

Original languageEnglish
Pages (from-to)2474-2477
Number of pages4
JournalEpilepsia
Volume51
Issue number12
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Dravet syndrome
  • Intrafamilial heterogeneity
  • MLPA
  • SCN9A
  • Seizures

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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    Guerrini, R., Cellini, E., Mei, D., Metitieri, T., Petrelli, C., Pucatti, D., Marini, C., & Zamponi, N. (2010). Variable epilepsy phenotypes associated with a familial intragenic deletion of the SCN1A gene. Epilepsia, 51(12), 2474-2477. https://doi.org/10.1111/j.1528-1167.2010.02790.x