Searchable abstracts of presentations at key conferences in endocrinology

ea0038pl4biog | Society for Endocrinology Dale Medal Lecture | SFEBES2015

Society for Endocrinology Dale Medal Lecture

Thakker Rajesh V

Rajesh Thakker is the May Professor of Medicine at the University of Oxford, UK. He received his medical degree from the University of Cambridge in 1980, and from 1981 to 1988 he undertook postgraduate clinical and research training at The Middlesex Hospital, The Hammersmith (Royal Postgraduate Medical School, RPMS), Hospital, and Northwick Park (MRC Clinical Research Centre) Hospital (London). In 1988, he was appoint...

ea0050p046 | Bone and Calcium | SFEBES2017

Systematic in silico evaluation of rare genetic variants in G-protein alpha 11 (Gα11)

Gluck Anna , Gorvin Caroline M , Thakker Rajesh V

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor (GPCR) that maintains systemic calcium homeostasis by detecting alterations in extracellular calcium, which it transduces into signalling changes, mainly via the Gq/11 pathway, leading to a decrease in PTH secretion. The importance of CaSR is highlighted by studies of patients that harbour germline CaSR mutations, which lead to a gain of receptor function in autosomal dominant...

ea0050p046 | Bone and Calcium | SFEBES2017

Systematic in silico evaluation of rare genetic variants in G-protein alpha 11 (Gα11)

Gluck Anna , Gorvin Caroline M , Thakker Rajesh V

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor (GPCR) that maintains systemic calcium homeostasis by detecting alterations in extracellular calcium, which it transduces into signalling changes, mainly via the Gq/11 pathway, leading to a decrease in PTH secretion. The importance of CaSR is highlighted by studies of patients that harbour germline CaSR mutations, which lead to a gain of receptor function in autosomal dominant...

ea0013oc18 | Novartis Clinical Endocrinology Award | SFEBES2007

Sedlin mutations disrupt interactions with pituitary homeobox 1 (Pitx1) and steroidogenic factor 1 (SF1): potential cause of delayed puberty in boys with Spondyloepiphyseal dysplasia tarda (SEDT)

Jeyabalan Jeshmi , Andrew Nesbit M , Ingraham Holly A , Thakker Rajesh V

Delayed puberty may occur in some boys affected with X-linked Spondyloepiphyseal dysplasia tarda (SEDT), which is caused by mutations of the gene encoding a 140 amino acid protein designated Sedlin. Sedlin interacts with the pituitary homeobox 1 (Pitx1) and steroidogenic factor 1 (SF1) transcription factors, which are involved in the development and regulation of the hypothalamic-pituitary-gonadal axis. We have therefore investigated the hypothesis that SEDT associated mutatio...

ea0055p27 | Poster Presentations | SFEEU2018

A case of Idiopathic Infantile Hypercalcaemia (IIH) persisting into adulthood, caused by compound heterozygous mutations of 1,25-dihydroxyvitamin D2 24-hydroxylase (CYP24A1)

Stokes Victoria , Gorvin Caroline M , Jafar-Mohammadi Bahram , Ryan Fiona , Thakker Rajesh V

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...

ea0050oc6.6 | Bone, Calcium and Neoplasia | SFEBES2017

Calcium-sensing receptor (CaSR) mutations in hypercalcaemic and hypocalcaemic patients cluster at the extracellular dimer interface

Olesen Mie K , Gorvin Caroline M , Thakker Rajesh V , Hannan Fadil M

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...

ea0050p242 | Neoplasia, Cancer and Late Effects | SFEBES2017

Combination of JQ1, an inhibitor of epigenetic pathways, and everolimus for treatment of pancreatic and bronchial neuroendocrine tumours

Lines Kate E , Stevenson Mark , Filippakopoulos Panagis , Grozinsky-Glasberg Simona , Bountra Chas , Thakker Rajesh V

Current treatments, including surgery, medical therapy, radiotherapy, and radionuclide therapy for neuroendocrine tumours of the pancreas (PNETs) and bronchus (BNETs) are often unsatisfactory, leading to a 5-year survival of <50% and 5%, respectively. PNETs and BNETs frequently have mutations in chromatin-remodelling genes and the protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, menin. Menin binds the...

ea0050oc6.6 | Bone, Calcium and Neoplasia | SFEBES2017

Calcium-sensing receptor (CaSR) mutations in hypercalcaemic and hypocalcaemic patients cluster at the extracellular dimer interface

Olesen Mie K , Gorvin Caroline M , Thakker Rajesh V , Hannan Fadil M

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...

ea0050p242 | Neoplasia, Cancer and Late Effects | SFEBES2017

Combination of JQ1, an inhibitor of epigenetic pathways, and everolimus for treatment of pancreatic and bronchial neuroendocrine tumours

Lines Kate E , Stevenson Mark , Filippakopoulos Panagis , Grozinsky-Glasberg Simona , Bountra Chas , Thakker Rajesh V

Current treatments, including surgery, medical therapy, radiotherapy, and radionuclide therapy for neuroendocrine tumours of the pancreas (PNETs) and bronchus (BNETs) are often unsatisfactory, leading to a 5-year survival of <50% and 5%, respectively. PNETs and BNETs frequently have mutations in chromatin-remodelling genes and the protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, menin. Menin binds the...

ea0086p42 | Endocrine Cancer and Late Effects | SFEBES2022

Hydroxymethylation is dysregulated in pancreatic neuroendocrine tumours and associated with aberrant DNA methylation

English Katherine A , Selberherr Andreas , Shariq Omair A , O'Neill Eric , Lines Kate W , Thakker Rajesh V

Pancreatic neuroendocrine tumours (PNETs) have a lower mutational burden than other tumours, indicating that other mechanisms contribute to tumourigenesis. One such reported mechanism is DNA methylome dysregulation, however, inconsistencies have been observed between gene methylation and protein expression, potentially stemming from the use of standard methylation assessment methods which do not distinguish methylation (5Â’methylcytosine (5Â’mC), repressive mark) from ...