TY - JOUR
T1 - Hypomagnesemia with secondary hypocalcemia is caused by mutations in TPRM6, a new member of the TPRM gene family
AU - Schlingmann, Karl P.
AU - Weber, Stefanie
AU - Peters, Melanie
AU - Nejsum, Lene Niemann
AU - Vitzthum, Helga
AU - Klingel, Karin
AU - Kratz, Markus
AU - Haddad, Elie
AU - Ristoff, Ellinor
AU - Dinour, Dganit
AU - Syrrou, Maria
AU - Nielsen, Søren
AU - Sassen, Martin
AU - Waldegger, Siegfried
AU - Seyberth, Hannsjörg W.
AU - Konrad, Martin
N1 - Funding Information:
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.
PY - 2002/6
Y1 - 2002/6
N2 - 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), previously mapped to chromosome 9q22 (ref. 3). The TRPM6 protein is a new member of the long transient receptor potential channel (TRPM) family 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 activity. 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.
AB - 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), previously mapped to chromosome 9q22 (ref. 3). The TRPM6 protein is a new member of the long transient receptor potential channel (TRPM) family 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 activity. 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.
UR - http://www.scopus.com/inward/record.url?scp=18544369466&partnerID=8YFLogxK
U2 - 10.1038/ng889
DO - 10.1038/ng889
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C2 - 12032568
AN - SCOPUS:18544369466
SN - 1061-4036
VL - 31
SP - 166
EP - 170
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -
