Loss of syntaxin 3 causes variant microvillus inclusion disease

Gastroenterology. 2014 Jul;147(1):65-68.e10. doi: 10.1053/j.gastro.2014.04.002. Epub 2014 Apr 12.

Abstract

Microvillus inclusion disease (MVID) is a disorder of intestinal epithelial differentiation characterized by life-threatening intractable diarrhea. MVID can be diagnosed based on loss of microvilli, microvillus inclusions, and accumulation of subapical vesicles. Most patients with MVID have mutations in myosin Vb that cause defects in recycling of apical vesicles. Whole-exome sequencing of DNA from patients with variant MVID showed homozygous truncating mutations in syntaxin 3 (STX3). STX3 is an apical receptor involved in membrane fusion of apical vesicles in enterocytes. Patient-derived organoid cultures and overexpression of truncated STX3 in Caco-2 cells recapitulated most characteristics of variant MVID. We conclude that loss of STX3 function causes variant MVID.

Keywords: Epithelial Polarity; Syntaxin 3; Variant Microvillus Inclusion Disease.

Publication types

  • Case Reports

MeSH terms

  • Biopsy
  • Caco-2 Cells
  • Duodenum / pathology
  • Female
  • Humans
  • Infant
  • Intestinal Mucosa / pathology
  • Malabsorption Syndromes / genetics*
  • Malabsorption Syndromes / pathology
  • Male
  • Microvilli / genetics
  • Microvilli / pathology*
  • Mucolipidoses / genetics*
  • Mucolipidoses / pathology
  • Mutation / genetics*
  • Organ Culture Techniques
  • Qa-SNARE Proteins / genetics*

Substances

  • Qa-SNARE Proteins

Supplementary concepts

  • Microvillus inclusion disease