Abstract
Magnesium is an essential ion involved in many biochemical and physiological processes. Homeostasis of magnesium levels is tightly regulated and depends on the balance between intestinal absorption and renal excretion. However, little is known about specific proteins mediating transepithelial magnesium transport. Using a positional candidate gene approach, we identified mutations in TRPM6 (also known as CHAK2), encoding TRPM6, in autosomal-recessive hypomagnesemia with secondary hypocalcemia (HSH, OMIM 602014)1,2, previously mapped to chromosome 9q22 (ref. 3). The TRPM6 protein is a new member of the long transient receptor potential channel (TRPM) family4 and is highly similar to TRPM7 (also known as TRP-PLIK), a bifunctional protein that combines calcium- and magnesium-permeable cation channel properties with protein kinase activity5,6,7. TRPM6 is expressed in intestinal epithelia and kidney tubules. These findings indicate that TRPM6 is crucial for magnesium homeostasis and implicate a TRPM family member in human disease.
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Acknowledgements
We thank the patients and their families for participating in this study, U. Pechmann and P. Barth for excellent technical assistance, C. Antignac, R. Preisig-Müller, C. Derst and N. Jeck for helpful discussions and C. Loirat, D. Lotan, W. Scheurlen, A. Siamopoulou, S. Alfandaki, G. Celsi and A. Kernell for providing clinical data. S.W., H.W.S. and M.K. were supported by the Deutsche Forschungsgemeinschaft. S.W. was supported by the Kempkes-Stiftung, University of Marburg. L.N.N. and S.N. were supported by the Danish National Research Foundation.
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Schlingmann, K., Weber, S., Peters, M. et al. Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet 31, 166–170 (2002). https://doi.org/10.1038/ng889
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DOI: https://doi.org/10.1038/ng889
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