Brief Communication

De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy†

  1. Fadi F. Hamdan PhD1,
  2. Amélie Piton PhD2,
  3. Julie Gauthier PhD2,
  4. Anne Lortie MD1,
  5. François Dubeau MD3,
  6. Sylvia Dobrzeniecka MSc2,
  7. Dan Spiegelman MSc2,
  8. Anne Noreau MSc2,
  9. Stéphanie Pellerin RN1,
  10. Mélanie Côté BSc2,
  11. Edouard Henrion MSc2,
  12. Éric Fombonne MD4,
  13. Laurent Mottron MD, PhD5,
  14. Claude Marineau MSc, MBA2,
  15. Pierre Drapeau PhD6,
  16. Ronald G. Lafrenière PhD2,
  17. Jean Claude Lacaille PhD7,
  18. Guy A. Rouleau MD, PhD2,
  19. Jacques L. Michaud MD1,*

Article first published online: 18 MAR 2009

DOI: 10.1002/ana.21625

Issue

Annals of Neurology

Annals of Neurology

Volume 65, Issue 6, pages 748–753, June 2009

Additional Information

How to Cite

Hamdan, F. F., Piton, A., Gauthier, J., Lortie, A., Dubeau, F., Dobrzeniecka, S., Spiegelman, D., Noreau, A., Pellerin, S., Côté, M., Henrion, E., Fombonne, É., Mottron, L., Marineau, C., Drapeau, P., Lafrenière, R. G., Lacaille, J. C., Rouleau, G. A. and Michaud, J. L. (2009), De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy. Annals of Neurology, 65: 748–753. doi: 10.1002/ana.21625

Author Information

  1. 1

    Centre of Excellence in Neuromics of Université de Montréal and Synapse to Disease Group, Centre Hospitalier Universitaire Sainte-Justine Research Center, Université de Montréal, Montreal, Quebec, Canada

  2. 2

    Centre Hospitalier de L'Université de Montréal Research Center and Department of Medicine, Université de Montréal, Montreal, Quebec, Canada

  3. 3

    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

  4. 4

    Department of Psychiatry, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada

  5. 5

    Centre de Recherche Fernand-Séguin, Hôpital Rivière-des-Prairies, Université de Montréal, Montreal, Quebec, Canada

  6. 6

    Department of Pathology and Cell Biology, Le Groupe de Recherche sur le Système Nerveux Central and Le Groupe Fonds de la Recherche en Santé du Quebec de Recherche sur le Système Nerveux Central, Université de Montréal, Montreal, Quebec, Canada

  7. 7

    Department of Physiology, Le Groupe de Recherche sur le Système Nerveux Central and Le Groupe Fonds de la Recherche en Santé du Quebec de Recherche sur le Système Nerveux Central, Université de Montréal, Montreal, Quebec, Canada

*Research Center, CHU Sainte-Justine, 3175 Côte Sainte-Catherine, Montreal, Quebec, Canada H3T 1C5

  1. †

    Potential conflict of interest: Nothing to report.

Publication History

  1. Issue published online: 25 JUN 2009
  2. Article first published online: 18 MAR 2009
  3. Accepted manuscript online: 18 MAR 2009 12:00AM EST
  4. Manuscript Accepted: 5 DEC 2008
  5. Manuscript Revised: 10 NOV 2008
  6. Manuscript Received: 26 SEP 2008

Funded by

  • Canadian Institute of Health Research. Grant Number: GMH-79079
  • Fonds de la Recherche en Santé (FRSQ)
  • Genome Canada and Genome Quebec and Université de Montréal for the Synapse to Diseases (S2D) project
  • Clinical Investigatorship Award of the Canadian Institute of Health Research (Institute of Genetics)

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (288K)

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. Ann Neurol 2009;65:748–753

View Full Article with Supporting Information (HTML) Get PDF (288K)