RGD Reference Report - Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. - Rat Genome Database

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Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia.

Authors: Groenestege, WM  Thebault, S  Van der Wijst, J  Van den Berg, D  Janssen, R  Tejpar, S  Van den Heuvel, LP  Van Cutsem, E  Hoenderop, JG  Knoers, NV  Bindels, RJ 
Citation: Groenestege WM, etal., J Clin Invest. 2007 Aug;117(8):2260-7.
RGD ID: 6906911
Pubmed: (View Article at PubMed) PMID:17671655
DOI: Full-text: DOI:10.1172/JCI31680

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.

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Egf  (epidermal growth factor)

Genes (Mus musculus)
Egf  (epidermal growth factor)

Genes (Homo sapiens)
EGF  (epidermal growth factor)

Additional Information