Recent Advances in Molecular Genetics of Hereditary Magnesium-Losing Disorders

Abstract

Abstract. Recent advances in molecular genetics in hereditary hypomagnesemia substantiated the role of a variety of genes and their encoded proteins in human magnesium transport mechanisms. This knowledge on underlying genetic defects helps to distinguish different clinical subtypes and gives first insight into molecular components involved in magnesium transport. By mutation analysis and functional protein studies, novel pathophysiologic aspects were elucidated. For some of these disorders, transgenic animal models were generated to study genotype-phenotype relations and disease pathology. This review will discuss genetic and clinical aspects of familial disorders associated with magnesium wasting and focuses on the recent progress that has been made in molecular genetics. Besides isolated renal forms of hereditary hypomagnesemia, the following disorders will also be presented: familial hypomagnesemia with hypercalciuria and nephrocalcinosis, hypomagnesemia with secondary hypocalcemia, Ca 2ϩ /Mg 2ϩ -sensing receptor-associated disorders, and disorders associated with renal salt-wasting and hypokalemic metabolic alkalosis, comprising the Gitelman syndrome and the Bartter-like syndromes.

CLDN16 Genotype Predicts Renal Decline in Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

“…The progressive tubulointerstitial nephropathy in FHHNC has been attributed to the concomitant hypercalciuria and nephrocalcinosis; however, other authors have questioned this explanation because many other disease states associated with early-onset nephrocalcinosis are not followed by a severe deterioration of renal function. 25,26 All patients with FHHNC are affected by marked medullary nephrocalcinosis, but their degree of renal insufficiency is varying to a great extent. The reason for this variation has been unknown.…”

Emerging roles of TRPM6/TRPM7 channel kinase signal transduction complexes

“…Mg 2+ plays a vital role in virtually all cellular pathways as a co-factor of many enzymes, an essential structural element of proteins and nucleic acids and a modulator of ion channels (Grubbs 2002;Konrad and Weber 2003;Konrad et al 2004;Romani and Maguire 2002;Wolf et al 2003). While free [Mg 2+ ] i was estimated to be between 0.5 and 1 mM, the total Mg 2+ content in the majority of cells was calculated to be in the range of 14-20 mM (Grubbs 2002;Konrad and Weber 2003;Konrad et al 2004;Romani and Maguire 2002;Wolf et al 2003). Intracellular Mg 2+ is mostly bound to ATP, other phosphonucleotides, phospholipids and proteins (Grubbs 2002;Romani and Scarpa 2000).…”

“…Nevertheless, Mg 2+ ions move into the cell primary driven by the electrical gradient. A variety of hormonal and metabolic stimuli tightly regulate [Mg 2+ ] i , a process involving at least two types of transport systems in the plasma membrane: extrusion of the cation by putative Na + /Mg 2+ or/and H + /Mg 2+ exchangers and its entry via Mg 2+ -permeable cation channels (Grubbs 2002;Konrad and Weber 2003;Konrad et al 2004;Romani and Maguire 2002;Wolf et al 2003).…”

An assay of some thermal characteristics, chemical and phytochemical constituents of <i>Hymenocarida acida</i> timber

“…Sodium and potassium play important role in maintenance of osmotic, electrolytic balance and proper rhythm of clothing (Tahiret al, 1999). Magnesium is for signaling the nervous system and also participates in osmotic and electrolyte balance but can cause genetic disorder (Konrad, and Weber, 2003). Copper is also involved in body enzymatic activities while zinc is required for growth, sexual development, wound healing infection, sense of taste and night vision in human (Maret and Sandstead, 2006).…”