title: Intellectual disability without epilepsy associated with STXBP1 disruption.
abstract: STXBP1 (Munc18-1) is a component of the machinery involved in the fusion of secretory vesicles to the presynaptic membrane for the release of neurotransmitters. De novo missense mutations in STXBP1 were recently reported in patients with Ohtahara syndrome, a form of encephalopathy with severe early-onset epilepsy. In addition, sequencing of the coding region of STXBP1 in 95 patients with non-syndromic intellectual disability (NSID) revealed de novo truncating mutations in two patients who also showed severe non-specific epilepsy, suggesting that STXBP1 disruption has the potential of causing a wide spectrum of epileptic disorders in association with intellectual disability. Here, we report on the mutational screening of STXBP1 in a different series of 50 patients with NSID and the identification of a novel de novo truncating mutation (c.1206delT/ p.Y402X) in a male with NSID, but surprisingly with no history of epilepsy. This is the first report of a patient with a truncating mutation in STXBP1 that does not show epilepsy, thus, expanding the clinical spectrum associated with STXBP1 disruption.
authors.affiliation: The Centre of Excellence in Neuromics of Université de Montréal and Synapse to Disease (S2D) group, Montréal, Quebec, Canada.
authors.forename: Fadi F
authors.initials: FF
authors.lastname: Hamdan
authors.forename: Julie
authors.initials: J
authors.lastname: Gauthier
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dobrzeniecka
authors.forename: Anne
authors.initials: A
authors.lastname: Lortie
authors.forename: Laurent
authors.initials: L
authors.lastname: Mottron
authors.forename: Michel
authors.initials: M
authors.lastname: Vanasse
authors.forename: Guy
authors.initials: G
authors.lastname: D'Anjou
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Lacaille
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: Jacques L
authors.initials: JL
authors.lastname: Michaud
mesh_terms: D000328:Adult; D004827:Epilepsy / Q000150:complications / Q000235:genetics; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008297:Male; D051938:Munc18 Proteins / Q000235:genetics*; D009154:Mutation; D055815:Young Adult
chemical_list: D051938:Munc18 Proteins; C497937:STXBP1 protein, human