Title: Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia
Authors: Groenestege, Wouter M. Tiel ×
Thebault, Stephanie
van der Wijst, Jenny
van den Berg, Dennis
Janssen, Rob
Tejpar, Sabine
van den Heuvel, Lambertus
Van Cutsem, Eric
Hoenderop, Joost G
Knoers, Nine V
Bindels, Rene J #
Issue Date: Aug-2007
Publisher: Amer soc clinical investigation inc
Series Title: Journal of Clinical Investigation vol:117 issue:8 pages:2260-2267
Abstract: Primary hypomagnesemia constitutes a rare heterogeneous group of disorders characterized by renal or intestinal magnesium (Mg2+) wasting resulting in generally shared symptoms of Mg2+ depletion, such as tetany and generalized convulsions, and often including associated disturbances in calcium excretion. However, most of the genes involved in the physiology of Mg2+ handling are unknown. Through the discovery of a mutation in the EGF gene in isolated autosomal recessive renal hypomagnesemia, we have, for what we believe is the first time, identified a magnesiotropic hormone crucial for total body Mg2+ balance. The mutation leads to impaired basolateral sorting of pro-EGF. As a consequence, the renal EGFR is inadequately stimulated, resulting in insufficient activation of the epithelial Mg2+ channel TRPM6 (transient receptor potential cation channel, subfamily M, member 6) and thereby Mg2+ loss. Furthermore, we show that colorectal cancer patients treated with cetuximab, an antagonist of the EGFR, develop hypomagnesemia, emphasizing the significance of EGF in maintaining Mg2+ balance.
ISSN: 0021-9738
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
Clinical Digestive Oncology (+)
Molecular Digestive Oncology (+)
× corresponding author
# (joint) last author

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