Loss of Syntaxin 3 Causes Variant Microvillus Inclusion Disease

C.L. Wiegerinck; A.R. Janecke; K. Schneeberger; G.F. Vogel; D.Y.  van Haaften-Visser; J.C. Escher; R. Adam; C.E. Thöni; K. Pfaller; A.J. Jordan; C.A. Weis; I.J. Nijman; G.R. Monroe; P.M. van Hasselt; E. Cutz; J. Klumperman; H.C. Clevers; E.E.S. Nieuwenhuis; R.H.J. Houwen; G.  van Haaften; M.W. Hess; L.A. Huber; J.M. Stapelbroek; T. Müller; S. Middendorp

doi:10.1053/j.gastro.2014.04.002

Loss of Syntaxin 3 Causes Variant Microvillus Inclusion Disease

C.L. Wiegerinck, A.R. Janecke, K. Schneeberger, G.F. Vogel, D.Y. van Haaften-Visser, J.C. Escher, R. Adam, C.E. Thöni, K. Pfaller, A.J. Jordan, C.A. Weis, I.J. Nijman, G.R. Monroe, P.M. van Hasselt, E. Cutz, J. Klumperman, H.C. Clevers, E.E.S. Nieuwenhuis, R.H.J. Houwen, G. van HaaftenM.W. Hess, L.A. Huber, J.M. Stapelbroek, T. Müller, S. Middendorp

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	65-U142
Number of pages	14
Journal	Gastroenterology
Volume	147
Issue number	1
DOIs	https://doi.org/10.1053/j.gastro.2014.04.002
Publication status	Published - 2014

Keywords

Variant Microvillus Inclusion Disease
Syntaxin 3
Epithelial Polarity
POLARIZED EPITHELIAL-CELLS
MUTATIONS
MYO5B

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10.1053/j.gastro.2014.04.002

http://www.sciencedirect.com/science/article/pii/S001650851400451X

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Wiegerinck, C. L., Janecke, A. R., Schneeberger, K., Vogel, G. F., van Haaften-Visser, D. Y., Escher, J. C., Adam, R., Thöni, C. E., Pfaller, K., Jordan, A. J., Weis, C. A., Nijman, I. J., Monroe, G. R., van Hasselt, P. M., Cutz, E., Klumperman, J., Clevers, H. C., Nieuwenhuis, E. E. S., Houwen, R. H. J., ... Middendorp, S. (2014). Loss of Syntaxin 3 Causes Variant Microvillus Inclusion Disease. Gastroenterology, 147(1), 65-U142. https://doi.org/10.1053/j.gastro.2014.04.002

@article{ccd787be54744a3b88466dbc15c15423,

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.",

keywords = "Variant Microvillus Inclusion Disease, Syntaxin 3, Epithelial Polarity, POLARIZED EPITHELIAL-CELLS, MUTATIONS, MYO5B",

author = "C.L. Wiegerinck and A.R. Janecke and K. Schneeberger and G.F. Vogel and {van Haaften-Visser}, D.Y. and J.C. Escher and R. Adam and C.E. Th{\"o}ni and K. Pfaller and A.J. Jordan and C.A. Weis and I.J. Nijman and G.R. Monroe and {van Hasselt}, P.M. and E. Cutz and J. Klumperman and H.C. Clevers and E.E.S. Nieuwenhuis and R.H.J. Houwen and {van Haaften}, G. and M.W. Hess and L.A. Huber and J.M. Stapelbroek and T. M{\"u}ller and S. Middendorp",

year = "2014",

doi = "10.1053/j.gastro.2014.04.002",

language = "English",

volume = "147",

pages = "65--U142",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders Ltd",

number = "1",

}

Wiegerinck, CL, Janecke, AR, Schneeberger, K, Vogel, GF, van Haaften-Visser, DY, Escher, JC, Adam, R, Thöni, CE, Pfaller, K, Jordan, AJ, Weis, CA, Nijman, IJ, Monroe, GR, van Hasselt, PM, Cutz, E, Klumperman, J, Clevers, HC, Nieuwenhuis, EES , Houwen, RHJ , van Haaften, G, Hess, MW, Huber, LA, Stapelbroek, JM, Müller, T & Middendorp, S 2014, 'Loss of Syntaxin 3 Causes Variant Microvillus Inclusion Disease', Gastroenterology, vol. 147, no. 1, pp. 65-U142. https://doi.org/10.1053/j.gastro.2014.04.002

TY - JOUR

T1 - Loss of Syntaxin 3 Causes Variant Microvillus Inclusion Disease

AU - Wiegerinck, C.L.

AU - Janecke, A.R.

AU - Schneeberger, K.

AU - Vogel, G.F.

AU - van Haaften-Visser, D.Y.

AU - Escher, J.C.

AU - Adam, R.

AU - Thöni, C.E.

AU - Pfaller, K.

AU - Jordan, A.J.

AU - Weis, C.A.

AU - Nijman, I.J.

AU - Monroe, G.R.

AU - van Hasselt, P.M.

AU - Cutz, E.

AU - Klumperman, J.

AU - Clevers, H.C.

AU - Nieuwenhuis, E.E.S.

AU - Houwen, R.H.J.

AU - van Haaften, G.

AU - Hess, M.W.

AU - Huber, L.A.

AU - Stapelbroek, J.M.

AU - Müller, T.

AU - Middendorp, S.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Variant Microvillus Inclusion Disease

KW - Syntaxin 3

KW - Epithelial Polarity

KW - POLARIZED EPITHELIAL-CELLS

KW - MUTATIONS

KW - MYO5B

U2 - 10.1053/j.gastro.2014.04.002

DO - 10.1053/j.gastro.2014.04.002

M3 - Article

C2 - 24726755

SN - 0016-5085

VL - 147

SP - 65-U142

JO - Gastroenterology

JF - Gastroenterology

IS - 1

ER -

Loss of Syntaxin 3 Causes Variant Microvillus Inclusion Disease

Abstract

Keywords

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