De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy.
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.
Hamdan
Fadi F
FF
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.
Piton
Amélie
A
Gauthier
Julie
J
Lortie
Anne
A
Dubeau
François
F
Dobrzeniecka
Sylvia
S
Spiegelman
Dan
D
Noreau
Anne
A
Pellerin
Stéphanie
S
Côté
Mélanie
M
Henrion
Edouard
E
Fombonne
Eric
E
Mottron
Laurent
L
Marineau
Claude
C
Drapeau
Pierre
P
Lafrenière
Ronald G
RG
Lacaille
Jean Claude
JC
Rouleau
Guy A
GA
Michaud
Jacques L
JL
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*
D051938:Munc18 Proteins; C497937:STXBP1 protein, human