Loss-of-function mutations of STXBP1 in patients with epileptic encephalopathy

Brain Dev. 2016 Mar;38(3):280-4. doi: 10.1016/j.braindev.2015.09.004. Epub 2015 Sep 16.

Abstract

Epileptic encephalopathy, which commences during early infancy, is a severe epileptic syndrome that manifests as age-dependent seizures and severe developmental delay. The syntaxin-binding protein 1 gene (STXBP1) is one of the genes responsible for epileptic encephalopathy. We conducted a cohort study to analyze STXBP1 in 42 patients with epileptic encephalopathy. We identified four novel mutations: two splicing mutations, a frameshift mutation, and a nonsense mutation. All of these mutations were predicted to cause loss-of-function. This result suggests loss-of-function is a common mechanism underlying STXBP1-related epileptic encephalopathy. The four patients showed epileptic features consistent with STXBP1-related epileptic encephalopathy, but showed variable radiological findings, including brain volume loss and myelination delay.

Keywords: Loss-of-function; Ohtahara syndrome; STXBP1-related epileptic encephalopathy; West syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / physiopathology
  • Child
  • Child, Preschool
  • Codon, Nonsense*
  • Cohort Studies
  • Electroencephalography
  • Female
  • Frameshift Mutation*
  • Humans
  • Infant
  • Male
  • Munc18 Proteins / genetics*
  • Munc18 Proteins / metabolism
  • Mutation
  • RNA Splicing
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / metabolism

Substances

  • Codon, Nonsense
  • Munc18 Proteins
  • STXBP1 protein, human