Recurrent FXYD2 p.Gly41Arg Mutation in Patients With Isolated Dominant Hypomagnesaemia

Nephrol Dial Transplant. 2015 Jun;30(6):952-7. doi: 10.1093/ndt/gfv014. Epub 2015 Mar 11.

Abstract

Background: Magnesium (Mg(2+)) is an essential ion for cell growth, neuroplasticity and muscle contraction. Blood Mg(2+) levels <0.7 mmol/L may cause a heterogeneous clinical phenotype, including muscle cramps and epilepsy and disturbances in K(+) and Ca(2+) 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.

Keywords: FXYD2; Na+–K+-ATPase; distal convoluted tubule; kidney; magnesium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Genes, Dominant
  • Homeostasis / genetics
  • Humans
  • Hypercalciuria / genetics*
  • Hypercalciuria / metabolism
  • Magnesium / blood*
  • Male
  • Mutation / genetics*
  • Nephrocalcinosis / genetics*
  • Nephrocalcinosis / metabolism
  • Pedigree
  • Renal Tubular Transport, Inborn Errors / genetics*
  • Renal Tubular Transport, Inborn Errors / metabolism
  • Sodium-Potassium-Exchanging ATPase / genetics*
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • FXYD2 protein, human
  • Sodium-Potassium-Exchanging ATPase
  • Magnesium

Supplementary concepts

  • Hypomagnesemia primary