Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia

Nat Genet. 2002 Jun;31(2):171-4. doi: 10.1038/ng901. Epub 2002 May 28.


Familial hypomagnesemia with secondary hypocalcemia (OMIM 602014) is an autosomal recessive disease that results in electrolyte abnormalities shortly after birth. Affected individuals show severe hypomagnesemia and hypocalcemia, which lead to seizures and tetany. The disorder has been thought to be caused by a defect in the intestinal absorption of magnesium, rather than by abnormal renal loss of magnesium. Restoring the concentrations of serum magnesium to normal values by high-dose magnesium supplementation can overcome the apparent defect in magnesium absorption and in serum concentrations of calcium. Life-long magnesium supplementation is required to overcome the defect in magnesium handling by these individuals. We previously mapped the gene locus to chromosome 9q in three large inbred kindreds from Israel. Here we report that mutation of TRPM6 causes hypomagnesemia with secondary hypocalcemia and show that individuals carrying mutations in this gene have abnormal renal magnesium excretion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA Mutational Analysis
  • Humans
  • Hypocalcemia / etiology
  • Hypocalcemia / genetics*
  • Ion Channels / genetics*
  • Magnesium / blood*
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Sequence Analysis, DNA
  • TRPM Cation Channels


  • Ion Channels
  • TRPM Cation Channels
  • TRPM6 protein, human
  • Magnesium

Associated data

  • GENBANK/AF350881
  • GENBANK/AL354795
  • GENBANK/BC022929
  • GENBANK/BE465471
  • OMIM/602014
  • RefSeq/NM_017662