STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern

Epilepsia. 2010 Dec;51(12):2397-405. doi: 10.1111/j.1528-1167.2010.02728.x. Epub 2010 Sep 30.


Purpose: De novo STXBP1 mutations have been found in individuals with early infantile epileptic encephalopathy with suppression-burst pattern (EIEE). Our aim was to delineate the clinical spectrum of subjects with STXBP1 mutations, and to examine their biologic aspects.

Methods: STXBP1 was analyzed in 29 and 54 cases of cryptogenic EIEE and West syndrome, respectively, as a second cohort. RNA splicing was analyzed in lymphoblastoid cells from a subject harboring a c.663 + 5G>A mutation. Expression of STXBP1 protein with missense mutations was examined in neuroblastoma2A cells.

Results: A total of seven novel STXBP1 mutations were found in nine EIEE cases, but not in West syndrome. The mutations include two frameshift mutations, three nonsense mutations, a splicing mutation, and a recurrent missense mutation in three unrelated cases. Including our previous data, 10 of 14 individuals (71%) with STXBP1 aberrations had the onset of spasms after 1 month, suggesting relatively later onset of epileptic spasms. Nonsense-mediated mRNA decay associated with abnormal splicing was demonstrated. Transient expression revealed that STXBP1 proteins with missense mutations resulted in degradation in neuroblastoma2A cells.

Discussion: Collectively, STXBP1 aberrations can account for about one-third individuals with EIEE (14 of 43). These genetic and biologic data clearly showed that haploinsufficiency of STXBP1 is the important cause for cryptogenic EIEE.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / physiopathology
  • Electroencephalography / statistics & numerical data*
  • Epilepsy, Generalized / diagnosis
  • Epilepsy, Generalized / genetics*
  • Epilepsy, Generalized / physiopathology
  • Female
  • Haploinsufficiency / genetics*
  • Haploinsufficiency / physiology
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Munc18 Proteins / genetics*
  • Mutation, Missense / genetics*
  • Mutation, Missense / physiology
  • Spasms, Infantile / diagnosis
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / physiopathology


  • Munc18 Proteins
  • STXBP1 protein, human