Impaired Basolateral Sorting of Pro-egf Causes Isolated Recessive Renal Hypomagnesemia.
From: Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
The Journal of clinical investigation
- Publish Date: Aug 2007
- ISSN: 0021-9738
- Volume: 117
- Issue: 8
- Pages: 2260-7
- Medium: Print
- Language: English
- Citation (JAMA): Groenestege Wouter M Tiel, Thébault Stéphanie, van der Wijst Jenny, et al. Impaired Basolateral Sorting of Pro-egf Causes Isolated Recessive Renal Hypomagnesemia.. J. Clin. Invest. Aug 2007;117:2260-7
Abstract
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.
Mesh Headings (Keywords): Animals, Antibodies, Monoclonal, Antineoplastic Agents, Colorectal Neoplasms, Epidermal Growth Factor, Female, Humans, Kidney, Magnesium, Male, Mutation, Pedigree, Protein Precursors, Protein Processing, Post-Translational, Receptor, Epidermal Growth Factor, Renal Tubular Transport, Inborn Errors, TRPM Cation Channels, Tetany
Check for Full Text / PubMed Unique Identifier (PMID): 17671655
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