Endocrine Abstracts

Hereditary hypercalcaemia can be a diagnostic challenge. We present a family with autosomal dominant hypercalcaemia that illustrates this. A 48-year-old man was referred with asymptomatic long standing hypercalcaemia (2.8–3.04 mmol/l), with plasma PTH levels between 45 and 48 ng/l (normal 15–65), and a high urinary calcium excretion, (24 h calcium collection 10.4 mmol/l (2.5–7.5), with high calcium excretion indexes) all consistent with primary hyperparathyroidi...

Mutational analysis of the calcium-sensing receptor (CaSR) is frequently undertaken to confirm a diagnosis of familial hypocalciuric hypercalcaemia (FHH) and autosomal dominant hypocalcaemic hypercalciuria (ADHH). However, functional characterization of these CaSR mutations to demonstrate loss-of-function for FHH mutations and gain-of-function for ADHH mutations is infrequently performed. We demonstrate the importance of pursuing in vitro studies that investigate the functiona...

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...

The autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome is an autosomal recessive disorder characterized by immune deficiency and the autoimmune destruction of endocrine organs such as the parathyroids, adrenal cortex and ovaries. APECED is caused by biallelic germline mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3, which is expressed in thymic medullary epithelial cells and plays a key role ...

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...

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...

The autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome is an autosomal recessive disorder characterized by immune deficiency and the autoimmune destruction of endocrine organs such as the parathyroids, adrenal cortex and ovaries. APECED is caused by biallelic germline mutations of the autoimmune regulator (AIRE) gene on chromosome 21q22.3, which is expressed in thymic medullary epithelial cells and plays a key role ...

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...

Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder characterised by hypercalcaemia and inappropriately low renal calcium excretion. FHH can be classified into three types: FHH1, caused by calcium-sensing receptor (CaSR) loss-of-function mutations, accounting for >65% of cases; FHH2, due to loss-of-function mutations of the G-protein α11 subunit (Gα11); and FHH3, resulting from loss-of-function mutations in the adap...

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...