GNAS and Hypocalcemia: Due to loss-of-function mutations of GNAS or methylation alteration in differentially methylated regions (DMRs), defected or loss of expression of α-subunit of heterotrimeric guanine-binding protein (Gsα) will reduce the response to PTH at proximal renal tubule, a GNAS imprinted expression tissue, defecting calcium reabsorption and 1,25-dihydroxy vitamin D synthesis, thus causing hypocalcemia and elevated PTH level as negative feedback [1].