Jeroen H F de Baaij1, Eiske M Dorresteijn2, Eric A M Hennekam3, Erik-Jan Kamsteeg4, Rowdy Meijer4, Karin Dahan5, Michelle Muller6, Marinus A van den Dorpel7, René J M Bindels1, Joost G J Hoenderop1, Olivier Devuyst8, Nine V A M Knoers3. 1. Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. 2. Pediatric Nephrology, Erasmus MC, Sophia Childrens Hospital, Rotterdam, The Netherlands. 3. Department of Medical Genetics, University Medical Centre Utrecht, Utrecht 3508 AB, The Netherlands. 4. Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. 5. Institut de Génétique et de Pathologie, IPG, Gosselies, Belgium. 6. Centre Hospitalier Peltzer-La Tourelle, Verviers, Belgium. 7. Department of Internal Medicine, Maasstad Hospital, Rotterdam, The Netherlands. 8. Institute of Physiology, ZIHP, University of Zurich, Zürich, Switzerland.
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.
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.Gly41ArgFXYD2 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.Gly41ArgFXYD2 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: Andreas Kompatscher; Jeroen H F de Baaij; Karam Aboudehen; Anke P W M Hoefnagels; Peter Igarashi; René J M Bindels; Gertjan J C Veenstra; Joost G J Hoenderop Journal: Kidney Int Date: 2017-05-31 Impact factor: 10.612
Authors: Daan Viering; Karl P Schlingmann; Marguerite Hureaux; Tom Nijenhuis; Andrew Mallett; Melanie M Y Chan; André van Beek; Albertien M van Eerde; Jean-Marie Coulibaly; Marion Vallet; Stéphane Decramer; Solenne Pelletier; Günter Klaus; Martin Kömhoff; Rolf Beetz; Chirag Patel; Mohan Shenoy; Eric J Steenbergen; Glenn Anderson; Ernie M H F Bongers; Carsten Bergmann; Daan Panneman; Richard J Rodenburg; Robert Kleta; Pascal Houillier; Martin Konrad; Rosa Vargas-Poussou; Nine V A M Knoers; Detlef Bockenhauer; Jeroen H F de Baaij Journal: J Am Soc Nephrol Date: 2021-10-04 Impact factor: 10.121
Authors: Gijs A C Franken; Dominik Müller; Cyril Mignot; Boris Keren; Jonathan Lévy; Anne-Claude Tabet; David Germanaud; María-Isabel Tejada; Hester Y Kroes; Rutger A J Nievelstein; Elise Brimble; Maria Ruzhnikov; Felix Claverie-Martin; Maria Szczepańska; Martin Ćuk; Femke Latta; Martin Konrad; Luis A Martínez-Cruz; René J M Bindels; Joost G J Hoenderop; Karl-Peter Schlingmann; Jeroen H F de Baaij Journal: Hum Mutat Date: 2021-03-01 Impact factor: 4.878
Authors: Daan H H M Viering; Jeroen H F de Baaij; Stephen B Walsh; Robert Kleta; Detlef Bockenhauer Journal: Pediatr Nephrol Date: 2016-05-27 Impact factor: 3.714
Authors: Jeroen H F de Baaij; Francisco J Arjona; Michiel van den Brand; Marla Lavrijsen; Anke L L Lameris; René J M Bindels; Joost G J Hoenderop Journal: Sci Rep Date: 2016-06-28 Impact factor: 4.379