mTOR-Activating Mutations in RRAGD Are Causative for Kidney Tubulopathy and Cardiomyopathy.
Karl-Peter SchlingmannFrançois JouretKuang ShenAnukrati NigamFrancisco J ArjonaClaudia DafingerPascal HouillierDeborah P JonesFelix KleinerüschkampJun OhNathalie GodefroidMehmet EltanTülay GüranStéphane BurteyMarie-Christine ParotteJens KönigAlina BraunCaro BosMaria Ibars SerraHolger RehmannFried J T ZwartkruisKirsten Y RenkemaKarin KlingelEric Schulze-BahrBernhard SchermerCarsten BergmannJanine AltmüllerHolger ThieleBodo Bernhard BeckKarin DahanDavid SabatiniMax Christoph LiebauRosa Vargas-PoussouNine V A M KnoersMartin KonradJeroen H F de BaaijPublished in: Journal of the American Society of Nephrology : JASN (2021)
Our findings establish a novel disease, which we call autosomal dominant kidney hypomagnesemia (ADKH-RRAGD), that combines an electrolyte-losing tubulopathy and dilated cardiomyopathy. The condition is caused by variants in the RRAGD gene, which encodes Rag GTPase D; these variants lead to an activation of mTOR signaling, suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function.