Article: Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia.
The Journal of clinical investigation
2007 Volume 117, Issue 8, Page(s) 2260–2267
Abstract: ... The mutation leads to impaired basolateral sorting of pro-EGF. As a consequence, the renal EGFR is inadequately ... of a mutation in the EGF gene in isolated autosomal recessive renal hypomagnesemia, we have, for what we believe ... Primary hypomagnesemia constitutes a rare heterogeneous group of disorders characterized by renal ...
| 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. |
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| MeSH term(s) | Animals ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Cetuximab ; Colorectal Neoplasms/complications ; Colorectal Neoplasms/drug therapy ; Epidermal Growth Factor/genetics ; Epidermal Growth Factor/metabolism ; Female ; Humans ; Kidney/metabolism ; Magnesium/metabolism ; Male ; Mutation ; Pedigree ; Protein Precursors/genetics ; Protein Precursors/metabolism ; Protein Processing, Post-Translational/drug effects ; Protein Processing, Post-Translational/genetics ; Receptor, Epidermal Growth Factor/genetics ; Receptor, Epidermal Growth Factor/metabolism ; Renal Tubular Transport, Inborn Errors/chemically induced ; Renal Tubular Transport, Inborn Errors/genetics ; Renal Tubular Transport, Inborn Errors/metabolism ; TRPM Cation Channels/biosynthesis ; TRPM Cation Channels/genetics ; Tetany/chemically induced ; Tetany/genetics ; Tetany/metabolism | |||||
| Chemical Substances | Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Protein Precursors ; TRPM Cation Channels ; TRPM6 protein, human ; epidermal growth factor precursor ; Epidermal Growth Factor (62229-50-9) ; EGFR protein, human (EC 2.7.10.1) ; Receptor, Epidermal Growth Factor (EC 2.7.10.1) ; Magnesium (I38ZP9992A) ; Cetuximab (PQX0D8J21J) | |||||
| Language | English | |||||
| Publishing date | 2007-08 | |||||
| Publishing country | United States | |||||
| Document type | Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 3067-3 | |||||
| ISSN | 1558-8238 ; 0021-9738 | |||||
| ISSN (online) | 1558-8238 | |||||
| ISSN | 0021-9738 | |||||
| DOI | 10.1172/JCI31680 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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