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.