De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy

Ann Neurol. 2009 Jun;65(6):748-53. doi: 10.1002/ana.21625.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Epilepsy / complications
  • Epilepsy / diagnosis
  • Epilepsy / genetics*
  • Female
  • Humans
  • Intellectual Disability / complications
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Munc18 Proteins / genetics*
  • Mutation / genetics*


  • Munc18 Proteins
  • STXBP1 protein, human