Searchable abstracts of presentations at key conferences in endocrinology

ea0041gp1 | Adrenal | ECE2016

The role of primary cilia in the molecular pathogenesis of phaeochromocytoma

O'Toole Samuel , Srirangalingam Umasuthan , Drake William , Chapple J Paul

Phaeochromocytomas are neuroendocrine tumours arising from adrenal medulla chromaffin cells. They are life threatening due to adrenaline and noradrenaline release and potential for metastatic spread. Understanding of phaeochromocytoma pathogenesis is incomplete with limited ability to predict malignant potential. Additionally, once metastatic, response to conventional therapies is disappointing.Phaeochromocytomas are a common feature of the inherited can...

ea0051oc5.3 | Oral Communications 5 | BSPED2017

Novel evidence implies that ALADIN, the triple A syndrome gene product is involved in mitochondrial physiology

Da Costa Alexandra Rodrigues , Meimaridou Eirini , Prasad Rathi , Metherell Louise A. , Chapple J. Paul , Storr Helen L.

Triple A syndrome (AAAS), a rare and debilitating autosomal recessive disorder. It is characterised by adrenal failure, alacrima and achalasia; ~70% patients develop a neurodegeneration. The AAAS gene encodes ALADIN, a nuclear pore complex (NPC) protein necessary for the selective nuclear import of DNA protective molecules and is important for cellular redox homeostasis. ALADIN’s role is not fully characterised: its discovery at the centrosome and the endoplasmic...

ea0015oc6 | Young Endocrinologist prize session | SFEBES2008

MRAP2 permits the functional expression of the melanocortin-2-receptor: a new member of a new family of melanocortin receptor accessory proteins

Chan Li , Metherell Louise , Elphick Maurice , Chapple J Paul , Clark Adrian

Background: The identification of MRAP in 2005 as the first melanocortin-2-receptor (MC2R)/ACTH receptor accessory protein provided insight into the regulation of the melanocortin receptor system. Mutations in MRAP cause Familial glucocorticoid deficiency, an autosomal recessive disorder resulting in isolated cortisol deficiency. In vitro studies showed that MRAP was essential for the functional expression of the MC2R. The melanocortin receptor (MCR) family (MC1R to MC5...

ea0009oc26 | Oral Communication 4: Steroids | BES2005

Identification of a defective gene in Familial Glucocorticoid Deficiency type 2 as a ACTH receptor accessory factor responsible for cell surface trafficking

Metherell L , Chapple J , Cooray S , Naville D , Begeot M , Huebner A , Cheetham M , Clark A

FGD is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex to stimulate glucocorticoid production. The disease is caused by mutations in ACTHR or MC2R in 25% of cases, termed FGD type 1, and has previously been linked to a locus on chromosome 8q12.2-21.2 in a single family with FGD type 2. We have recently described a novel gene (FGD2) that when defective is a second cause of FGD. Sequencing of this gene in 100 FGD2 patients ha...

ea0058oc5.3 | Oral Communications 5 | BSPED2018

Can novel stem cell models help unpick the pathogenesis of the Triple A syndrome?

Costa Alexandra Rodrigues Da , Qarin Shamma , Bradshaw Teisha , Watson David , Prasad Rathi , Metherell Louise A , Barnes Michael R , Skarnes William , Chapple J Paul , Storr Helen L

Triple A syndrome (AAAS) is a rare, incurable, homozygous disorder, characterised by tissue-specific degeneration resulting in adrenal failure and neurodisability. The AAAS gene encodes ALADIN, a nuclear pore complex (NPC) protein necessary for nuclear import of DNA protective molecules, important for redox homeostasis. ALADIN’s role is not fully characterised: its discovery at the centrosome and the endoplasmic reticulum suggests a role outside the NPC. The inte...