Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome - Inria - Institut national de recherche en sciences et technologies du numérique Access content directly
Journal Articles Journal of Medical Genetics Year : 2010

Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome

Oriane Trouillard
Denis Graber
  • Function : Author
  • PersonId : 889734
Nathalie Villeneuve
  • Function : Author
  • PersonId : 889737
Marie-Odile Livet
  • Function : Author
  • PersonId : 889738
Claude Adam
  • Function : Author
  • PersonId : 889740
Sophie Dupont
  • Function : Author
  • PersonId : 889741
Delphine Héron
  • Function : Author
  • PersonId : 889742

Abstract

Background. Mutations in SCN1A can cause Genetic Epilepsy with Febrile Seizures Plus (GEFS+, inherited missense mutations) or Dravet syndrome (DS, de novo mutations of all types). Although the mutational spectra are distinct, these disorders share major features and 10% of DS patients have an inherited SCN1A mutation. Objectives and patients. We studied 19 selected families with at least one DS patients to describe the mechanisms accounting for inherited SCN1A mutations in DS. The mutation identified in the DS probands was searched in available parents and relatives and quantified in the blood cells of the transmitting parent using quantitative allele-specific assays. Results. Mosaicism in the blood cells of the transmitting parent was demonstrated in 12 cases and suspected in another case. The proportion of mutated allele in the blood varied from 0.04% to 85%. In the 6 remaining families, six novel missense mutations were associated with autosomal dominant variable GEFS+ phenotypes including DS as the more severe clinical picture. Conclusion. Our results indicate that mosaicism is found in at least 7% of families with at least one DS patient and that it accounts for 68 % (13/19) of inherited mutations associated with DS. On the contrary, in the remaining cases (6/19, 32%), the patients were part of multiplex GEFS+ families and seemed to represent the extreme end of the GEFS+ clinical spectrum. In this latter case, additional genetic or environmental factors likely modulate the severity of the expression of the mutation.
Fichier principal
Vignette du fichier
PEER_stage2_10.1136%2Fjmg.2009.074328.pdf (793.3 Ko) Télécharger le fichier
Origin : Files produced by the author(s)
Loading...

Dates and versions

hal-00557383 , version 1 (19-01-2011)

Identifiers

Cite

Christel Depienne, Oriane Trouillard, Isabelle Gourfinkel-An, Cécile Saint-Martin, Delphine Bouteiller, et al.. Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome. Journal of Medical Genetics, 2010, 47 (6), pp.404. ⟨10.1136/jmg.2009.074328⟩. ⟨hal-00557383⟩
746 View
727 Download

Altmetric

Share

Gmail Facebook X LinkedIn More