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MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity

Abstract

Following homozygosity mapping in a single kindred, we identified nonsense and missense mutations in MYO5B, encoding type Vb myosin motor protein, in individuals with microvillus inclusion disease (MVID). MVID is characterized by lack of microvilli on the surface of enterocytes and occurrence of intracellular vacuolar structures containing microvilli. In addition, mislocalization of transferrin receptor in MVID enterocytes suggests that MYO5B deficiency causes defective trafficking of apical and basolateral proteins in MVID.

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Figure 1: Immunofluorescence of jejunal biopsy samples from four different individuals with MYO5B mutations and a control individual.

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Acknowledgements

We thank S. Steiner, V. Wild, K. Gutleben, A. Flörl, T. Erdel and D. Hilber for technical assistance. The work was supported by the Austrian Science Funds (FWF), grants P18470 to A.R.J., SFB021 to L.A.H., P19486-B12 to M.W.H., Jubiläumsfonds grant P-11050 and support from TILAK-Universitätskliniken to M.W.H., a Dr.-Legerlotz-Stiftung grant to A.R.J. and a grant by Raiffeisen Landesbank-Tirol AG to T.M.

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Correspondence to Andreas R Janecke.

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Müller, T., Hess, M., Schiefermeier, N. et al. MYO5B mutations cause microvillus inclusion disease and disrupt epithelial cell polarity. Nat Genet 40, 1163–1165 (2008). https://doi.org/10.1038/ng.225

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