Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6 , a new member of the TRPM gene family

• Published in: Nature genetics Vol. 31; no. 2; pp. 166 - 170
• Main Authors: Sassen, Martin, Kratz, Markus, Haddad, Elie, Syrrou, Maria, Konrad, Martin, Weber, Stefanie, Niemann Nejsum, Lene, Klingel, Karin, Nielsen, Søren, Ristoff, Ellinor, Peters, Melanie, Vitzthum, Helga, Dinour, Dganit, Waldegger, Siegfried, Seyberth, Hannsjörg W, Schlingmann, Karl P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.06.2002
• Subjects: Absorption; Adult; Biological and medical sciences; Calcium; CHAK2 gene; Chromosomes; Cloning; Complications and side effects; Diagnosis; Excretion; Female; Fundamental and applied biological sciences. Psychology; Gene mutations; Genes; Genes. Genome; Haplotypes; Homeostasis; Humans; Hypocalcemia; Hypocalcemia - etiology; Hypocalcemia - genetics; Infant; Infant, Newborn; Ion Channels - genetics; Ion Channels - physiology; Kidneys; Kinases; Magnesium; Magnesium - blood; Magnesium deficiency diseases; Male; Medicin och hälsovetenskap; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Multigene Family - genetics; Mutation; Pediatrics; Pedigree; Physiology; Proteins; Risk factors; Sequence Analysis, DNA; transient receptor potential protein; TRPM Cation Channels; TRPM6 gene; Germany; Sweden; Turkey; Israel; Albania; Metabolic disorder; Hydroelectrolytic balance disorder; Secondary; Calcium; Multigene family; Magnesium; Mutation; Inorganic element; Hypocalcemia; Hypomagnesemia
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng889

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.