Loss of syntaxin 3 causes variant microvillus inclusion disease.

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.

• Authors: Caroline L Wiegerinck, Andreas R Janecke, Kerstin Schneeberger, Georg F Vogel, Désirée Y van Haaften-Visser, Johanna C Escher, Rüdiger Adam, Cornelia E Thöni, Kristian Pfaller, Alexander J Jordan, Cleo-Aron Weis, Isaac J Nijman, Glen R Monroe, Peter M van Hasselt, Ernest Cutz, Judith Klumperman, Hans Clevers, Edward E S Nieuwenhuis, Roderick H J Houwen, Gijs van Haaften, Michael W Hess, Lukas A Huber, Janneke M Stapelbroek, Thomas Müller, Sabine Middendorp
• Journal: Gastroenterology (Gastroenterology) Vol. 147 Issue 1 Pg. 65-68.e10 (Jul 2014) ISSN: 1528-0012 [Electronic] United States
• PMID: 24726755 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Qa-SNARE Proteins

Topics

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