Background. Magnesium (Mg2+) is an essential ion for cell growth, neuroplasticity and muscle contraction. Blood Mg2+ levels <0.7 mmol/L may cause a heterogeneous clinical phenotype, including muscle cramps and epilepsy and disturbances in K+ and Ca2+ homeostasis. Over the last decade, the genetic origin of several familial forms of hypomagnesaemia has been found. In 2000, mutations in FXYD2, encoding the γ-subunit of the Na+-K+-ATPase, were identified to cause isolated dominant hypomagnesaemia (IDH) in a large Dutch family suffering from hypomagnesaemia, hypocalciuria and chondrocalcinosis. However, no additional patients have been identified since then. Methods. Here, two families with hypomagnesaemia and hypocalciuria were screened for mutations in the FXYD2 gene. Moreover, the patients were clinically and genetically characterized. Results. We report a p.Gly41Arg FXYD2 mutation in two families with hypomagnesaemia and hypocalciuria. Interestingly, this is the same mutation as was described in the original study. As in the initial family, several patients suffered from muscle cramps, chondrocalcinosis and epilepsy. Haplotype analysis revealed an overlapping haplotype in all families, suggesting a founder effect. Conclusions. The recurrent p.Gly41Arg FXYD2 mutation in two new families with IDH confirms that FXYD2 mutation causes hypomagnesaemia. Until now, no other FXYD2 mutations have been reported which could indicate that other FXYD2 mutations will not cause hypomagnesaemia or are embryonically lethal.

distal convoluted tubule, FXYD2, kidney, magnesium, Na+-K+-ATPase
dx.doi.org/10.1093/ndt/gfv014, hdl.handle.net/1765/90874
Nephrology, Dialysis, Transplantation
This work was funded by the European Commission 7th Framework Programme; grant id fp7/305608 - European Consortium for High-Throughput Research in Rare Kidney Diseases (EURENOMICS)
Department of Pediatrics

de Baaij, J.H.F, Dorresteijn, E.M, Hennekam, R.C.M, Kamsteeg, E.J, Meijer, R, Dahan, K, … Knoers, N.V.A.M. (2015). Recurrent FXYD2 p.Gly41Arg mutation in patients with isolated dominant hypomagnesaemia. Nephrology, Dialysis, Transplantation, 30(6), 952–957. doi:10.1093/ndt/gfv014