De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy

Fadi F. Hamdan, Amélie Piton, Julie Gauthier, Anne Lortie, François Dubeau, Sylvia Dobrzeniecka, Dan Spiegelman, Anne Noreau, Stéphanie Pellerin, Mélanie Côté, Edouard Henrion, Eric Fombonne, Laurent Mottron, Claude Marineau, Pierre Drapeau, Ronald G. Lafrenière, Jean Claude Lacaille, Guy A. Rouleau, Jacques L. Michaud

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

We sequenced genes coding for components of the SNARE complex (STX1A, VAMP2, SNAP25) and their regulatory proteins (STXBP1/Munc18-1, SYT1), which are essential for neurotransmission, in 95 patients with idiopathic mental retardation. We identified de novo mutations in STXBP1 (nonsense, p.R388X; splicing, c.169+1G>A) in two patients with severe mental retardation and nonsyndromic epilepsy. Reverse transcriptase polymerase chain reaction and sequencing showed that the splicing mutation creates a stop codon downstream of exon-3. No de novo or deleterious mutations in STXBP1 were found in 190 control subjects, or in 142 autistic patients. These results suggest that STXBP1 disruption is associated with autosomal dominant mental retardation and nonsyndromic epilepsy.

Original languageEnglish (US)
Pages (from-to)748-753
Number of pages6
JournalAnnals of Neurology
Volume65
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

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Intellectual Disability
Epilepsy
Mutation
Munc18 Proteins
Vesicle-Associated Membrane Protein 2
Gene Components
SNARE Proteins
Terminator Codon
Reverse Transcriptase Polymerase Chain Reaction
Synaptic Transmission
Exons

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Hamdan, F. F., Piton, A., Gauthier, J., Lortie, A., Dubeau, F., Dobrzeniecka, S., ... Michaud, J. L. (2009). De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy. Annals of Neurology, 65(6), 748-753. https://doi.org/10.1002/ana.21625

De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy. / Hamdan, Fadi F.; Piton, Amélie; Gauthier, Julie; Lortie, Anne; Dubeau, François; Dobrzeniecka, Sylvia; Spiegelman, Dan; Noreau, Anne; Pellerin, Stéphanie; Côté, Mélanie; Henrion, Edouard; Fombonne, Eric; Mottron, Laurent; Marineau, Claude; Drapeau, Pierre; Lafrenière, Ronald G.; Lacaille, Jean Claude; Rouleau, Guy A.; Michaud, Jacques L.

In: Annals of Neurology, Vol. 65, No. 6, 06.2009, p. 748-753.

Research output: Contribution to journalArticle

Hamdan, FF, Piton, A, Gauthier, J, Lortie, A, Dubeau, F, Dobrzeniecka, S, Spiegelman, D, Noreau, A, Pellerin, S, Côté, M, Henrion, E, Fombonne, E, Mottron, L, Marineau, C, Drapeau, P, Lafrenière, RG, Lacaille, JC, Rouleau, GA & Michaud, JL 2009, 'De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy', Annals of Neurology, vol. 65, no. 6, pp. 748-753. https://doi.org/10.1002/ana.21625
Hamdan FF, Piton A, Gauthier J, Lortie A, Dubeau F, Dobrzeniecka S et al. De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy. Annals of Neurology. 2009 Jun;65(6):748-753. https://doi.org/10.1002/ana.21625
Hamdan, Fadi F. ; Piton, Amélie ; Gauthier, Julie ; Lortie, Anne ; Dubeau, François ; Dobrzeniecka, Sylvia ; Spiegelman, Dan ; Noreau, Anne ; Pellerin, Stéphanie ; Côté, Mélanie ; Henrion, Edouard ; Fombonne, Eric ; Mottron, Laurent ; Marineau, Claude ; Drapeau, Pierre ; Lafrenière, Ronald G. ; Lacaille, Jean Claude ; Rouleau, Guy A. ; Michaud, Jacques L. / De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy. In: Annals of Neurology. 2009 ; Vol. 65, No. 6. pp. 748-753.
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