title: Recurrent FXYD2 p.Gly41Arg mutation in patients with isolated dominant hypomagnesaemia.
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.
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jeroen H F
authors.initials: JH
authors.lastname: de Baaij
authors.affiliation: Pediatric Nephrology, Erasmus MC, Sophia Childrens Hospital, Rotterdam, The Netherlands.
authors.forename: Eiske M
authors.initials: EM
authors.lastname: Dorresteijn
authors.affiliation: Department of Medical Genetics, University Medical Centre Utrecht, Utrecht 3508 AB, The Netherlands.
authors.forename: Eric A M
authors.initials: EA
authors.lastname: Hennekam
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Erik-Jan
authors.initials: EJ
authors.lastname: Kamsteeg
authors.affiliation: Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Rowdy
authors.initials: R
authors.lastname: Meijer
authors.affiliation: Institut de Génétique et de Pathologie, IPG, Gosselies, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Dahan
authors.affiliation: Centre Hospitalier Peltzer-La Tourelle, Verviers, Belgium.
authors.forename: Michelle
authors.initials: M
authors.lastname: Muller
authors.affiliation: Department of Internal Medicine, Maasstad Hospital, Rotterdam, The Netherlands.
authors.forename: Marinus A
authors.initials: MA
authors.lastname: van den Dorpel
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: René J M
authors.initials: RJ
authors.lastname: Bindels
authors.affiliation: Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Joost G J
authors.initials: JG
authors.lastname: Hoenderop
authors.affiliation: Institute of Physiology, ZIHP, University of Zurich, Zürich, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Devuyst
authors.affiliation: Department of Medical Genetics, University Medical Centre Utrecht, Utrecht 3508 AB, The Netherlands.
authors.forename: Nine V A M
authors.initials: NV
authors.lastname: Knoers
mesh_terms: D000328:Adult; D005260:Female; D005799:Genes, Dominant; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D053565:Hypercalciuria / Q000235:genetics* / Q000378:metabolism; D008274:Magnesium / Q000097:blood*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009397:Nephrocalcinosis / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism
chemical_list: C416502:FXYD2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium
keywords: FXYD2; Na+–K+-ATPase; distal convoluted tubule; kidney; magnesium