Endocrine Abstracts

Case History: X-linked hypophosphataemia (XLH) manifests as rickets in infancy or childhood, and is caused by mutations of the phosphate-regulating neutral endopeptidase (PHEX) gene, which leads to excess production of the fibroblast growth factor-23 (FGF-23) hormone. We present a case illustrating that mutation of PHEX can also cause hypophosphataemia presenting in adulthood. The proband is a 56-year-old male, who was referred with persistent hypophosphataem...

The CaSR, a G-protein-coupled receptor that regulates extracellular calcium (Ca2+o), predominantly signals via G-protein-αq/11 (Gαq/11), initiating IP3-mediated intracellular calcium (Ca2+i) accumulation, and mitogen-activated protein kinase (MAPK) signalling. CaSR also activates MAPK signalling via Gαi/o, or by associating with the scaffolding protein β-arrestin. CaSR g...

Adaptor protein-2 (AP2) is a heterotetramer of α, β, μ, and σ subunits that is pivotal in clathrin-mediated endocytosis and facilitates internalisation of plasma membrane constituents such as the calcium-sensing receptor (CaSR). AP2 σ subunit (AP2σ) missense mutations (Arg15Cys, Arg15His and Arg15Leu) result in familial hypocalciuric hypercalcaemia type 3 (FHH3) and decrease the sensitivity of CaSR-expressing cells to changes in extracellular calc...

The calcium-sensing receptor (CaSR) is a guanine-nucleotide-binding protein (G-protein)-coupled receptor that has a central role in calcium homeostasis. Loss-of-function mutations of the CaSR result in familial hypocalciuric hypercalcemia type 1 (FHH1) and loss-of-function coding mutations in the CaSR-associated G-protein subunit Gα11 have been reported to cause FHH2 in only two patients to date. The aim of our study was therefore to characterise additional <em...

Autosomal dominant hypocalcaemia (ADH) is a disorder that needs to be distinguished from hypoparathyroidism, as ADH patients are at risk of nephrocalcinosis and renal failure when treated with activated vitamin D preparations. ADH types 1 and 2 are due to gain-of-function mutations of the calcium-sensing receptor (CaSR) and G-protein α 11 (Gα11), respectively. CaSR targeted drugs, known as calcilytics, rectify the gain-of-function associated with ADH1-causing mutatio...

The calcium-sensing receptor (CaSR) is a guanine-nucleotide-binding protein (G-protein)-coupled receptor that has a central role in calcium homeostasis. Loss-of-function mutations of the CaSR result in familial hypocalciuric hypercalcemia type 1 (FHH1) and gain-of-function mutations in autosomal dominant hypocalcemia (ADH). Recently, loss-of-function Gα11 mutations have been identified to cause FHH2 and we hypothesised that gain-of-function Gα11...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor that regulates extracellular calcium concentration. The CaSR is also implicated in the pathogenesis of non-calcium disorders such as vascular calcification and diabetes, which are leading causes of cardiovascular disease. Common CaSR single nucleotide polymorphisms (SNPs) have been demonstrated to be determinants of calcium metabolism. The aim of this study was to investigate whether CaSR SNPs may influence va...

The calcium sensing receptor (CaSR) is a G protein coupled receptor that is expressed in type A intercalated cells of the distal convoluted tubule and cortical collecting ducts, where it is involved in renal proton excretion. We have therefore investigated the Nuf mouse, which has an activating CaSR mutation (Leu723Gln) that leads to hypocalcaemia, hypercalciuria, renal calcification, a urinary concentrating defect, and cataracts, for disturbances in acid-base homeostasis. Mic...

The calcium-sensing receptor (CaSR) is a G protein coupled receptor that is expressed widely, including pancreatic beta cells where it has been shown to modulate insulin secretion in vitro. However, the role of the CaSR in regulating in vivo insulin secretion and glucose homeostasis remains unknown. We have therefore investigated the Nuf mouse, which has an activating CaSR mutation (Leu723Gln), to determine whether abnormal CaSR function in vivo affects gl...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder of mineral metabolism that is characterized by lifelong elevation of serum calcium concentrations associated with inappropriately low urinary calcium excretion (calcium clearance:creatinine clearance <0.01). Three separate FHH loci have been identified (FHH1-3). Loss-of-function mutations of the calcium-sensing receptor (CaSR) gene located on 3q21.1, which account for the majority of FHH c...