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Elkadri A, Thoeni C, Deharvengt SJ, et al. Mutations in Plasmalemma Vesicle Associated Protein Result in Sieving Protein-Losing Enteropathy Characterized by Hypoproteinemia, Hypoalbuminemia, and Hypertriglyceridemia. Cell Mol Gastroenterol Hepatol. 2015;1(4):381-394.e7doi: 10.1016/j.jcmgh.2015.05.001.
Elkadri, A., Thoeni, C., Deharvengt, S. J., Murchie, R., Guo, C., Stavropoulos, J. D., Marshall, C. R., Wales, P., Bandsma, R., Cutz, E., Roifman, C. M., Chitayat, D., Avitzur, Y., Stan, R. V., & Muise, A. M. (2015). Mutations in Plasmalemma Vesicle Associated Protein Result in Sieving Protein-Losing Enteropathy Characterized by Hypoproteinemia, Hypoalbuminemia, and Hypertriglyceridemia. Cellular and molecular gastroenterology and hepatology, 1(4), 381-394.e7. https://doi.org/10.1016/j.jcmgh.2015.05.001
Elkadri, Abdul, et al. "Mutations in Plasmalemma Vesicle Associated Protein Result in Sieving Protein-Losing Enteropathy Characterized by Hypoproteinemia, Hypoalbuminemia, and Hypertriglyceridemia." Cellular and molecular gastroenterology and hepatology vol. 1,4 (2015): 381-394.e7. doi: https://doi.org/10.1016/j.jcmgh.2015.05.001
Elkadri A, Thoeni C, Deharvengt SJ, Murchie R, Guo C, Stavropoulos JD, Marshall CR, Wales P, Bandsma R, Cutz E, Roifman CM, Chitayat D, Avitzur Y, Stan RV, Muise AM. Mutations in Plasmalemma Vesicle Associated Protein Result in Sieving Protein-Losing Enteropathy Characterized by Hypoproteinemia, Hypoalbuminemia, and Hypertriglyceridemia. Cell Mol Gastroenterol Hepatol. 2015 Jul;1(4):381-394.e7. doi: 10.1016/j.jcmgh.2015.05.001. PMID: 26207260; PMCID: PMC4507283.
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Cell Mol Gastroenterol Hepatol. 2015 Jul;1(4):381-394.e7. doi: 10.1016/j.jcmgh.2015.05.001.

Mutations in Plasmalemma Vesicle Associated Protein Result in Sieving Protein-Losing Enteropathy Characterized by Hypoproteinemia, Hypoalbuminemia, and Hypertriglyceridemia.

Cellular and molecular gastroenterology and hepatology

Abdul Elkadri, Cornelia Thoeni, Sophie J Deharvengt, Ryan Murchie, Conghui Guo, James D Stavropoulos, Christian R Marshall, Paul Wales, Robert Bandsma, Ernest Cutz, Chaim M Roifman, David Chitayat, Yaron Avitzur, Radu V Stan, Aleixo M Muise

Affiliations

  1. SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada ; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada ; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
  2. SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada ; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada.
  3. Department of Pathology, Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03756, USA.
  4. Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada.
  5. Genome Diagnostics, Department of Paediatric Laboratory Medicine The Hospital for Sick Children, Toronto, ON, Canada.
  6. Group for Improvement of Intestinal Function and Treatment (GIFT), Hospital for Sick Children, Toronto, Ontario, Canada.
  7. Division of Pathology, The Hospital for Sick Children, Toronto, Canada.
  8. Division of Immunology, Department of Pediatrics, University of Toronto The Hospital for Sick Children, Toronto, Canada.
  9. Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada.
  10. SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada ; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada ; Institute of Medical Science, University of Toronto, Toronto, ON, Canada ; Department of Biochemistry, University of Toronto, Toronto, ON, Canada.

PMID: 26207260 PMCID: PMC4507283 DOI: 10.1016/j.jcmgh.2015.05.001

Abstract

BACKGROUND & AIMS METHODS: Severe intestinal diseases observed in very young children are often the result of monogenic defects. We used whole exome sequencing (WES) to examine the genetic cause in a patient with a distinct severe form of protein losing enteropathy (PLE) characterized by hypoproteinemia, hypoalbuminemia, and hypertriglyceridemia.

METHODS: WES was performed at the Centre for Applied Genomics, Hospital for Sick Children, Toronto, Canada. Exome library preparation was performed using the Ion Torrent AmpliSeq RDY Exome Kit. Functional studies were carried out based on the identified mutation.

RESULTS: Using whole exome sequencing we identified a homozygous nonsense mutation (1072C>T; p.Arg358*) in the

CONCLUSIONS: PLVAP p.Arg358* mutation resulted in loss of PLVAP expression with subsequent deletion of the diaphragms of endothelial fenestrae leading to plasma protein extravasation, protein-losing enteropathy and ultimately death.

Keywords: IBD; PLE; PLVAP; Protein losing enteropathy; VEOIBD; and hypertriglyceridemia; endothelium; fenestrae; hypoalbuminemia; hypoproteinemia; monogenic diseases; very early onset IBD

Conflict of interest statement

The authors have no potential conflicts including financial, professional, or personal that are relevant to the manuscript.

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