Loss of syntaxin 3 causes variant microvillus inclusion disease

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

doi:10.1053/j.gastro.2014.04.002

Loss of syntaxin 3 causes variant microvillus inclusion disease

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 HaaftenMichael W. Hess, Lukas A. Huber, Janneke M. Stapelbroek, Thomas Müller, Sabine Middendorp

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145 Citations (Scopus)

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)	65-68.e10
Journal	Gastroenterology
Volume	147
Issue number	1
DOIs	https://doi.org/10.1053/j.gastro.2014.04.002
Publication status	Published - Jul 2014
Externally published	Yes

Keywords

Epithelial Polarity
Syntaxin 3
Variant Microvillus Inclusion Disease

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10.1053/j.gastro.2014.04.002

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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., Nieuwenhuis, E. E. S., Houwen, R. H. J., ... Middendorp, S. (2014). Loss of syntaxin 3 causes variant microvillus inclusion disease. Gastroenterology, 147(1), 65-68.e10. https://doi.org/10.1053/j.gastro.2014.04.002

@article{5a14a2e41e2b4f85b8f99b6d44d9a466,

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 = "Epithelial Polarity, Syntaxin 3, Variant Microvillus Inclusion Disease",

author = "Wiegerinck, {Caroline L.} and Janecke, {Andreas R.} and Kerstin Schneeberger and Vogel, {Georg F.} and {Van Haaften-Visser}, {D{\'e}sir{\'e}e Y.} and Escher, {Johanna C.} and R{\"u}diger Adam and Th{\"o}ni, {Cornelia E.} and Kristian Pfaller and Jordan, {Alexander J.} and Weis, {Cleo Aron} and Nijman, {Isaac J.} and Monroe, {Glen R.} and {Van Hasselt}, {Peter M.} and Ernest Cutz and Judith Klumperman and Hans Clevers and Nieuwenhuis, {Edward E.S.} and Houwen, {Roderick H.J.} and {Van Haaften}, Gijs and Hess, {Michael W.} and Huber, {Lukas A.} and Stapelbroek, {Janneke M.} and Thomas M{\"u}ller and Sabine Middendorp",

note = "Funding Information: Funding Supported in part by the Oesterreichische Nationalbank Jubil{\"a}umsfonds (14496 to T.M.), the Tiroler Wissenschaftsfonds (UNI-0404/1286 to A.R.J. and T.M.), the Austrian Science Funds FWF (SFB021 to L.A.H.), MCBO (PhD Program in Molecular Cell Biology and Oncology at the Innsbruck Medical University) fellowship (C.E.T.), and Wilhelmina Children's Hospital Fund (S.M.). ",

year = "2014",

month = jul,

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

language = "English",

volume = "147",

pages = "65--68.e10",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W.B. Saunders",

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, H, 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. 65-68.e10. https://doi.org/10.1053/j.gastro.2014.04.002

TY - JOUR

T1 - Loss of syntaxin 3 causes variant microvillus inclusion disease

AU - Wiegerinck, Caroline L.

AU - Janecke, Andreas R.

AU - Schneeberger, Kerstin

AU - Vogel, Georg F.

AU - Van Haaften-Visser, Désirée Y.

AU - Escher, Johanna C.

AU - Adam, Rüdiger

AU - Thöni, Cornelia E.

AU - Pfaller, Kristian

AU - Jordan, Alexander J.

AU - Weis, Cleo Aron

AU - Nijman, Isaac J.

AU - Monroe, Glen R.

AU - Van Hasselt, Peter M.

AU - Cutz, Ernest

AU - Klumperman, Judith

AU - Clevers, Hans

AU - Nieuwenhuis, Edward E.S.

AU - Houwen, Roderick H.J.

AU - Van Haaften, Gijs

AU - Hess, Michael W.

AU - Huber, Lukas A.

AU - Stapelbroek, Janneke M.

AU - Müller, Thomas

AU - Middendorp, Sabine

N1 - Funding Information: Funding Supported in part by the Oesterreichische Nationalbank Jubiläumsfonds (14496 to T.M.), the Tiroler Wissenschaftsfonds (UNI-0404/1286 to A.R.J. and T.M.), the Austrian Science Funds FWF (SFB021 to L.A.H.), MCBO (PhD Program in Molecular Cell Biology and Oncology at the Innsbruck Medical University) fellowship (C.E.T.), and Wilhelmina Children's Hospital Fund (S.M.).

PY - 2014/7

Y1 - 2014/7

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 - Epithelial Polarity

KW - Syntaxin 3

KW - Variant Microvillus Inclusion Disease

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U2 - 10.1053/j.gastro.2014.04.002

DO - 10.1053/j.gastro.2014.04.002

M3 - Article

C2 - 24726755

AN - SCOPUS:84902957441

SN - 0016-5085

VL - 147

SP - 65-68.e10

JO - Gastroenterology

JF - Gastroenterology

IS - 1

ER -

Loss of syntaxin 3 causes variant microvillus inclusion disease

Abstract

Keywords

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