Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia.
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.
Walder
Roxanne Y
RY
Department of Pediatrics and Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA.
Landau
Daniel
D
Meyer
Peter
P
Shalev
Hanna
H
Tsolia
Maria
M
Borochowitz
Zvi
Z
Boettger
Melanie Barbara
MB
Beck
Gretel E
GE
Englehardt
Richard K
RK
Carmi
Rivka
R
Sheffield
Val C
VC
D004252:DNA Mutational Analysis; D006801:Humans; D006996:Hypocalcemia / Q000209:etiology / Q000235:genetics*; D007473:Ion Channels / Q000235:genetics*; D008274:Magnesium / Q000097:blood*; D008969:Molecular Sequence Data; 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