Hereditary isolated renal magnesium loss maps to chromosome 11q23

Hypomagnesemia due to isolated renal magnesium loss has previously been dem onstrated in two presumably unrelated Dutch families with autosomal dominan t mode of inheritance. Patients with magnesium deficiency may suffer from t etany and convulsions, but the patients with hereditary renal magnesium was ting can also be clinically nonsymptomatic. In a genomewide linkage study, we first excluded a possible candidate region, on chromosome 9q, that encom passes the gene for intestinal hypomagnesemia with secondary hypocalcemia a nd, subsequently, found linkage to markers on chromosome 11q23. Detailed ha plotype analyses identified a common haplotype segregating in both families , suggesting both their relationship through a common ancestor and the exis tence of a single, hypomagnesemia-causing mutation within them. The maximum two-point LOD score (Z(max)) was found for marker D11S4127 (Z(max) = 6.41 at a recombination fraction of .00),whereas a multipoint analysis gave a Z( max) of 8.24 between markers D11S4142 and D11S4171, Key recombination event s define a 5.6-cM region between these two markers on chromosome 11q23. We conclude that this region encompasses a gene, involved in renal magnesium h andling, that is mutated in our patients and is different from the gene inv olved in intestinal magnesium handling.