title: 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.affiliation: Division of Pediatrics, Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Wiegerinck
authors.affiliation: Division of Human Genetics, Biocenter Innsbruck, Innsbruck, Austria; Department of Pediatrics I, Biocenter Innsbruck, Innsbruck, Austria.
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Janecke
authors.affiliation: Division of Pediatrics, Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schneeberger
authors.affiliation: Division of Cell Biology, Biocenter Innsbruck, Innsbruck, Austria; Division of Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Vogel
authors.affiliation: Division of Pediatrics, Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Désirée Y
authors.initials: DY
authors.lastname: van Haaften-Visser
authors.affiliation: Pediatric Gastroenterology, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Escher
authors.affiliation: Pediatric Gastroenterology, Department of Pediatric and Adolescent Medicine, University Medical Centre, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Adam
authors.affiliation: Division of Cell Biology, Biocenter Innsbruck, Innsbruck, Austria; Division of Pathology, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada.
authors.forename: Cornelia E
authors.initials: CE
authors.lastname: Thöni
authors.affiliation: Division of Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Kristian
authors.initials: K
authors.lastname: Pfaller
authors.affiliation: Pediatric Gastroenterology, Department of Pediatric and Adolescent Medicine, University Medical Centre, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Jordan
authors.affiliation: Institute of Pathology, University Medical Centre, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Cleo-Aron
authors.initials: CA
authors.lastname: Weis
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Isaac J
authors.initials: IJ
authors.lastname: Nijman
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Glen R
authors.initials: GR
authors.lastname: Monroe
authors.affiliation: Division of Pediatrics, Department of Metabolic Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Peter M
authors.initials: PM
authors.lastname: van Hasselt
authors.affiliation: Division of Pathology, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada.
authors.forename: Ernest
authors.initials: E
authors.lastname: Cutz
authors.affiliation: Department of Cell Biology, University Medical Center Utrecht, Utrecht, The Netherlands; University Medical Center Utrecht, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Klumperman
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research, Royal Dutch Academy of Sciences, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: Division of Pediatrics, Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Edward E S
authors.initials: EE
authors.lastname: Nieuwenhuis
authors.affiliation: Division of Pediatrics, Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Roderick H J
authors.initials: RH
authors.lastname: Houwen
authors.affiliation: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Gijs
authors.initials: G
authors.lastname: van Haaften
authors.affiliation: Division of Histology and Embryology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Hess
authors.affiliation: Division of Cell Biology, Biocenter Innsbruck, Innsbruck, Austria.
authors.forename: Lukas A
authors.initials: LA
authors.lastname: Huber
authors.affiliation: Division of Pediatrics, Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Janneke M
authors.initials: JM
authors.lastname: Stapelbroek
authors.affiliation: Department of Pediatrics I, Biocenter Innsbruck, Innsbruck, Austria. Electronic address: thomas.mueller@uki.at.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.affiliation: Division of Pediatrics, Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: s.middendorp@umcutrecht.nl.
authors.forename: Sabine
authors.initials: S
authors.lastname: Middendorp
mesh_terms: D001706:Biopsy; D018938:Caco-2 Cells; D004386:Duodenum / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000473:pathology; D008286:Malabsorption Syndromes / Q000235:genetics* / Q000473:pathology; D008297:Male; D008871:Microvilli / Q000235:genetics / Q000473:pathology*; D009081:Mucolipidoses / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009924:Organ Culture Techniques; D050765:Qa-SNARE Proteins / Q000235:genetics*
chemical_list: D050765:Qa-SNARE Proteins
keywords: Epithelial Polarity; Syntaxin 3; Variant Microvillus Inclusion Disease