title: De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy.
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.
authors: 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.
authors: Fadi F
authors: FF
authors: Hamdan
authors: Amélie
authors: A
authors: Piton
authors: Julie
authors: J
authors: Gauthier
authors: Anne
authors: A
authors: Lortie
authors: François
authors: F
authors: Dubeau
authors: Sylvia
authors: S
authors: Dobrzeniecka
authors: Dan
authors: D
authors: Spiegelman
authors: Anne
authors: A
authors: Noreau
authors: Stéphanie
authors: S
authors: Pellerin
authors: Mélanie
authors: M
authors: Côté
authors: Edouard
authors: E
authors: Henrion
authors: Eric
authors: E
authors: Fombonne
authors: Laurent
authors: L
authors: Mottron
authors: Claude
authors: C
authors: Marineau
authors: Pierre
authors: P
authors: Drapeau
authors: Ronald G
authors: RG
authors: Lafrenière
authors: Jean Claude
authors: JC
authors: Lacaille
authors: Guy A
authors: GA
authors: Rouleau
authors: Jacques L
authors: JL
authors: Michaud
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D004827:Epilepsy / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D051938:Munc18 Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*
chemical_list: D051938:Munc18 Proteins; C497937:STXBP1 protein, human