Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family.
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.
Schlingmann
Karl P
KP
Department of Pediatrics, Philipps University of Marburg, Deutschhausstrasse 12, D-35037 Marburg, Germany.
Weber
Stefanie
S
Peters
Melanie
M
Niemann Nejsum
Lene
L
Vitzthum
Helga
H
Klingel
Karin
K
Kratz
Markus
M
Haddad
Elie
E
Ristoff
Ellinor
E
Dinour
Dganit
D
Syrrou
Maria
M
Nielsen
Søren
S
Sassen
Martin
M
Waldegger
Siegfried
S
Seyberth
Hannsjörg W
HW
Konrad
Martin
M
D000328:Adult; D005260:Female; D006239:Haplotypes; D006801:Humans; D006996:Hypocalcemia / Q000209:etiology / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D007473:Ion Channels / Q000235:genetics* / Q000502:physiology; D008274:Magnesium / Q000097:blood*; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D050053:TRPM Cation Channels
D007473:Ion Channels; D050053:TRPM Cation Channels; C459082:TRPM6 protein, human; D008274:Magnesium