Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemiaGroenestege, W. M. T., Thébault, S., van der Wijst, J., van den Berg, D., Janssen, R., Tejpar, S., van den Heuvel, L. P., van Cutsem, E., Hoenderop, J. G., Knoers, N. V. & Bindels, R. J., Aug-2007, In : The Journal of Clinical Investigation. 117, 8, p. 2260-2267 8 p.
Research output: Contribution to journal › Article › Academic › peer-review
Primary hypomagnesemia constitutes a rare heterogeneous group of disorders characterized by renal or intestinal magnesium (Mg(2+)) wasting resulting in generally shared symptoms of Mg(2+) 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 Mg(2+) 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 Mg(2+) 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 Mg(2+) channel TRPM6 (transient receptor potential cation channel, subfamily M, member 6) and thereby Mg(2+) 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 Mg(2+) balance.
|Number of pages||8|
|Journal||The Journal of Clinical Investigation|
|Publication status||Published - Aug-2007|
- Animals, Antibodies, Monoclonal/adverse effects, Antibodies, Monoclonal, Humanized, Antineoplastic Agents/adverse effects, Cetuximab, Colorectal Neoplasms/complications, Epidermal Growth Factor/genetics, ErbB Receptors/genetics, Female, Humans, Kidney/metabolism, Magnesium/metabolism, Male, Mutation, Pedigree, Protein Precursors/genetics, Protein Processing, Post-Translational/drug effects, Renal Tubular Transport, Inborn Errors/chemically induced, TRPM Cation Channels/biosynthesis, Tetany/chemically induced