title: Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family.
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), 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.
authors.affiliation: Department of Pediatrics, Philipps University of Marburg, Deutschhausstrasse 12, D-35037 Marburg, Germany.
authors.forename: Karl P
authors.initials: KP
authors.lastname: Schlingmann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Weber
authors.forename: Melanie
authors.initials: M
authors.lastname: Peters
authors.forename: Lene
authors.initials: L
authors.lastname: Niemann Nejsum
authors.forename: Helga
authors.initials: H
authors.lastname: Vitzthum
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.forename: Markus
authors.initials: M
authors.lastname: Kratz
authors.forename: Elie
authors.initials: E
authors.lastname: Haddad
authors.forename: Ellinor
authors.initials: E
authors.lastname: Ristoff
authors.forename: Dganit
authors.initials: D
authors.lastname: Dinour
authors.forename: Maria
authors.initials: M
authors.lastname: Syrrou
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Martin
authors.initials: M
authors.lastname: Sassen
authors.forename: Siegfried
authors.initials: S
authors.lastname: Waldegger
authors.forename: Hannsjörg W
authors.initials: HW
authors.lastname: Seyberth
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
mesh_terms: 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
chemical_list: D007473:Ion Channels; D050053:TRPM Cation Channels; C459082:TRPM6 protein, human; D008274:Magnesium