Nature Genetics
31, 171 - 174 (2002)
Published online: 28 May 2002; | doi:10.1038/ng901
Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemiaRoxanne Y. Walder1, Daniel Landau2, Peter Meyer3, Hanna Shalev2, Maria Tsolia4, Zvi Borochowitz5, Melanie Barbara Boettger3, Gretel E. Beck1, Richard K. Englehardt1, Rivka Carmi2
& Val C. Sheffield11
Department of Pediatrics and Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA. 2
Department of Pediatrics, Ben Gurion University, Beer Sheva, Israel. 3
Institute of Human Genetics, University of Heidelberg, INF 328, Heidelberg 69120, Germany. 4
Department of Pediatrics, P. & A. Kyriakou Children's Hospital, University of Athens, Athens, Greece. 5
Simon Winter Institute for Human Genetics, Bnai-Zion Medical Center, Haifa, Israel.
Correspondence should be addressed to Val C. Sheffield val-sheffield@uiowa.eduFamilial hypomagnesemia with secondary hypocalcemia (OMIM 602014) is an autosomal recessive disease that results in electrolyte abnormalities shortly after birth1,
2,
3,
4,
5,
6. 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 individuals1,
3,
4. We previously mapped the gene locus to chromosome 9q in three large inbred kindreds from Israel2. 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.
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