Rare Case of Pseudohypoparathyroidism With Normocalcemia Because of a Novel GNAS Mutation

Abstract

PTH resistance is characterized by hypocalcemia and hyperphosphatemia in the presence of elevated PTH concentrations, resulting in pseudohypoparathyroidism, which is subdivided into different types according to its different pathogenesis and phenotype. PTH receptor is the alpha subunit of stimulatory G protein (G _sα)-coupled receptor. Pathogenic variants of GNAS gene, encoding for G _sα, lead to reduced G _sα function and PTH resistance. We report a patient with PHP type 1a, with no documented evidence of hypocalcemia, presenting with AHO phenotype and multihormone resistance to PTH, TSH, and GnRH. Her genetic testing showed a novel heterozygous pathogenic variants, a c.934T > G change in exon 11 in adenylate cyclase stimulatory G protein that has not been reported in the literature so far.