Endocrine Abstracts

Familial hypocalciuric hypercalcaemia type-3 (FHH3) is caused by loss-of-function mutations of the sigma subunit of adaptor protein-2 (AP2), a ubiquitously expressed heterotetrameric protein with a fundamental role in endocytosis of transmembrane proteins. FHH3-associated AP2σ mutations impair internalisation of calcium-sensing receptor (CaSR) giving rise to FHH. CaSR predominantly signals via Gαq/11 leading to intracellular calcium release, and activation...

Case history: Idiopathic Infantile Hypercalcaemia (IIH) classically presents in the first year of life, usually resolves by 1 year of age and is due to mutations in 1,25-dihydroxyvitamin D2 24-hydroxylase (CYP24A1) or, rarely, sodium-phosphate cotransporter-2A (SLC34A1). We report a case of IIH in a Caucasian female, who was born to non-consanguineous parents, with hypercalcaemia, hypercalciuria and associated complications persisting into adulthoo...

Loss- and gain-of-function mutations of the calcium-sensing receptor (CaSR) cause familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemia (ADH), respectively. The CaSR is a homodimeric receptor that has a 612 amino acid extracellular domain (ECD), which binds extracellular calcium (Ca2+e) and mediates dimer interactions upon ligand binding. The ECD consists of lobes 1 and 2, and a cysteine-rich domain (CRD). To elucidate the struc...

Heterotrimeric G-proteins are important molecular switches that transduce extracellular ligand-binding at G-protein-coupled receptors (GPCRs) to intracellular signals. G-protein alpha-subunits (Gα) have two domains, a helical and GTPase domain, which provide structural stability and mediate GTPase activity, respectively. Gain-of-function Gα mutations cause endocrine conditions including McCune-Albright Syndrome, due to Gαs mutations, and a...

Hypoparathyroidism may occur as: a hereditary syndromic disorder (e.g. Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED), Hypoparathyroidism Sensorineural Deafness and Renal Disease (HDR), Autosomal Dominant Hypoparathyroidism type 1 (ADH1), or ADH type 2 (ADH2), which are due to mutations of autoimmune regulator (AIRE), GATA binding protein 3 (GATA3), calcium-sensing receptor (CASR) and G-protein sub...

Loss- and gain-of-function mutations of the calcium-sensing receptor (CaSR) cause familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemia (ADH), respectively. The CaSR is a homodimeric receptor that has a 612 amino acid extracellular domain (ECD), which binds extracellular calcium (Ca2+e) and mediates dimer interactions upon ligand binding. The ECD consists of lobes 1 and 2, and a cysteine-rich domain (CRD). To elucidate the struc...

Heterotrimeric G-proteins are important molecular switches that transduce extracellular ligand-binding at G-protein-coupled receptors (GPCRs) to intracellular signals. G-protein alpha-subunits (Gα) have two domains, a helical and GTPase domain, which provide structural stability and mediate GTPase activity, respectively. Gain-of-function Gα mutations cause endocrine conditions including McCune-Albright Syndrome, due to Gαs mutations, and a...

Hypoparathyroidism may occur as: a hereditary syndromic disorder (e.g. Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED), Hypoparathyroidism Sensorineural Deafness and Renal Disease (HDR), Autosomal Dominant Hypoparathyroidism type 1 (ADH1), or ADH type 2 (ADH2), which are due to mutations of autoimmune regulator (AIRE), GATA binding protein 3 (GATA3), calcium-sensing receptor (CASR) and G-protein sub...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor that predominantly signals via Gαq/11-mediated pathways to regulate extracellular calcium (Ca2+e) homeostasis. Germline Gα11 inactivating and activating mutations cause familial hypocalciuric hypercalcaemia type-2 (FHH2) and autosomal dominant hypocalcaemia type-2 (ADH2), respectively. To date, four FHH2 and six ADH2 mutations have been reported. To identif...

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...