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MYO5B Mutations in Patients With Microvillus Inclusion Disease Presenting With Transient Renal Fanconi Syndrome

Golachowska, Magdalena R.*; van Dael, Carin M.L.; Keuning, Hilda; Karrenbeld, Arend; Hoekstra, Dick*; Gijsbers, Carolien F.M.§; Benninga, Marc A.||; Rings, Edmond H.H.M.; van IJzendoorn, Sven C.D.*

Journal of Pediatric Gastroenterology and Nutrition: April 2012 - Volume 54 - Issue 4 - p 491–498
doi: 10.1097/MPG.0b013e3182353773
Original Articles: Gastroenterology

Background and Objective: Microvillus inclusion disease (MVID) is a rare congenital enteropathy associated with brush border atrophy and reduced expression of enzymes at the enterocytes’ apical surface. MVID is associated with mutations in the MYO5B gene, which is expressed in all epithelial tissues. Whether organs other than the intestine are affected in MVID is unclear. We report 2 patients with MVID that developed renal Fanconi syndrome while receiving total parenteral nutrition. Renal Fanconi syndrome has been correlated to apical plasma membrane defects in kidney proximal tubular epithelial cells. The aim of the present study was to determine whether MYO5B mutations in these patients correlate with similar apical plasma membrane defects in renal tubular epithelial cells as observed in the intestine.

Methods: Biopsies from kidney, duodenum, ileum, jejunum, and colon of 2 patients with MVID carrying MYO5B mutations and of age-matched controls were fixed in paraffin and analyzed with immunohistochemistry and transmission electron microscopy.

Results: Structural defects of the brush border and apical recycling endosome organization are observed in enterocytes of all of the segments of the small intestine and colon. MYO5B mutations in patients with MVID with renal Fanconi syndrome do not correlate with aberrant apical plasma membrane morphology or altered apical recycling endosome organization in renal tubular epithelial cells.

Conclusions: MYO5B mutations have divergent effects on the apical membrane system in kidney and intestinal epithelial cells. Epithelial defects presented in MVID are therefore likely triggered by intestine-specific factors, the identification of which may provide new targets and open avenues for the development of alternative therapeutic strategies to combat this devastating disease.

*Department of Cell Biology, Section of Membrane Cell Biology

Department of Pediatrics

Department of Pathology, University Medical Center Groningen, University of Groningen, Groningen

§Department of Pediatric Gastroenterology, Juliana Children's Hospital/Haga Teaching Hospital, The Hague

||Department of Pediatrics, Academic Medical Center Amsterdam, Amsterdam

VieCuri Medical Center, Venlo, The Netherlands.

Address correspondence and reprint requests to Sven C.D. van IJzendoorn, PhD, Department of Cell Biology, Section of Membrane Cell Biology, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands (e-mail:

Received 25 March, 2011

Accepted 8 August, 2011

Magdalena R. Golachowska and Carin M.L. van Dael should be considered joint first author. Edmond H.H.M. Rings and Sven C.D. van IJzendoorn should be considered joint last author.

This research was sponsored by the Dutch Digestive Disease Foundation (MLDS (WO 08–17)), the Jan Kornelis de Cock Foundation, and De Drie Lichten Foundation. M.G. was supported by the Ubbo Emmius Foundation. Sv.IJ. and E.R. were supported by the Royal Dutch Academy of Arts and Sciences.

The authors report no conflicts of interest.

Copyright 2012 by ESPGHAN and NASPGHAN