Ruling in a Suspect: The Role of AP2S1 Mutations in Familial Hypocalciuric Hypercalcemia Type 3

摘要

Roughly two-thirds of FHH cases are caused by heterozygous germline-inactivating mutations in the CASR gene (4, 5). In the parathyroid and renal tubular cells, where this G protein-coupled receptor (GPCR) is most abundantly expressed, direct calcium activation of the CaSR inhibits PTH secretion or decreases renal cal- cium reabsorption, respectively. Loss of function of one CASR allele in FHH reduces the sensitivity of the para- thyroid and renal cells to calcium and leads to hypercal- cemia and hypocalciuria (1). Homozygous loss-of-func- tion mutations of the CaSR cause severe neonatal hyperparathyroidism that can be lethal without parathy- roidectomy (6).