Searchable abstracts of presentations at key conferences in endocrinology

ea0063oc10.2 | Adrenal 2 | ECE2019

Glucocorticoid resistance patients exhibit defective cortisol metabolism, responsible for functional hypermineralocorticism

Vitellius Geraldine , Delemer Brigitte , Chabre Olivier , Caron Philippe , Pussard Eric , Bouligand Jerome , Trabado Severine , Lombes Marc

Glucocorticoid resistance syndrome, a rare genetic disease, is often associated with glucocorticoid receptor (GR) loss-of-function mutations. Six patients carrying heterozygous mutations of NR3C1 gene encoding GR, either missense R477S, Q501H, L672P or non-sense R469X, R491X, Y660X mutations were studied. Surprisingly, NR3C1 mutation carriers presented with low kalemia, low plasma renin and aldosterone levels associated or not with arterial hypertension, cons...

ea0063p1018 | Interdisciplinary Endocrinology 2 | ECE2019

MicroRNAs regulate aldosterone signaling by post-transcriptional control of mineralocorticoid receptor expression

Vu Thi-An , Lema Ingrid , Bouligand Jerome , Martinerie Laetitia , Lombes Marc , Viengchareun Say

The Mineralocorticoid Receptor (MR), a hormone-activated transcription factor that mediates sodium-retaining action of aldosterone, is highly expressed in the distal nephron in which large variations in extracellular fluid tonicity are generated by the cortico-papillary gradient. However, mechanisms regulating MR expression remain sparse. We recently showed that extracellular tonicity modulates renal MR expression through posttranscriptional mechanisms (Viengchareun, Mol Endoc...

ea0049gp45 | Bone & Calcium Homeostasis 2 | ECE2017

Methylation patterns at the novel DMR of GNAS (GNAS-AS2) in pseudohypoparathyroidism 1B (PHP1B or iPPSD3) subtypes

Hanna Patrick , Rochtus Anne , Jueppner Harald , Mackay Deborah , Francou Bruno , Bouligand Jerome , Mantel Anne , Anagnostou Elli , Gaillard Dominique , Linglart Agnes

PHP1B -iPPSD3 per the new proposed classification- is a rare disorder characterized in most patients by proximal tubular resistance to PTH resulting in hypocalcemia, hyperphosphatemia and elevated PTH. Loss-of-methylation (LOM) at the Differentially Methylated Region (DMR) at GNAS exon A/B occurs in all PHP1B patients, but methylation changes at other DMRs within GNAS occur in some familial and most sporadic PHP1B cases. All patients with autosomal dominant PHP1B (AD-...

ea0022h2.4 | Oral Communications Highlights 2 | ECE2010

TAC3 and TACR3 ‘Knockouts’ cause hypothalamic congenital hypogonadotropic hypogonadism in humans

Young Jacques , Bouligand Jerome , Francou Bruno , Raffin-Sanson Marie-Laure , Gaillez Stephanie , Jeanpierre Marc , Brailly-Tabard Sylvie , Guiochon-Mantel Anne

Missense loss-of-function mutations in TAC3 and TACR3, the genes encoding neurokinin B (NKB) and its receptor NK3R, respectively, were recently discovered in kindreds with non syndromic normosmic congenital hypogonadotropic hypogonadism (nCHH), thus identifying a fundamental role of this pathway in the human gonadotrope axis.We investigated the consequences on gonadotrope axis of TAC3 and TACR3 invalidations in adult patients ...

ea0022oc4.3 | Adrenals | ECE2010

Novel mutations in the glucocorticoid receptor gene: from familial bilateral adrenal hyperplasia to glucocorticoid receptor haploinsufficiency

Young Jacques , Trabado Severine , Bouligand Jerome , Amazit Larbi , Viengchareun Say , Guiochon-Mantel Anne , Delemer Brigitte , Lombes Marc

Glucocorticoid receptor (GR or NR3C1) is a ligand-dependent transcription factor that plays an essential role in differentiation, development, inflammatory responses and energy balance and is implicated in several human diseases. Eleven germinal GR mutations have been described so far, responsible for glucocorticoid resistance with variable clinical presentation.We report original heterozygous GR mutations in three independent patients, which have been i...

ea0049gp7 | Adrenal 1 | ECE2017

Identification of a new glucocorticoid receptor mutation underscores the substantial prevalence of genetic NR3C1 alterations in adrenal hyperplasia: the French National Research Program MUTA-GR

Vitellius Geraldine , Delemer Brigitte , Caron Philippe , Bennet Antoine , Bouligand Jerome , Guiochon-Mantel Anne , Viengchareun Say , Dani Christian , Trabado Severine , Lombes Marc

Primary generalized glucocorticoid resistance is characterized by glucocorticoid excess without any Cushing syndrome. Patients exhibit variable clinical presentation including arterial hypertension, hirsutism or adrenal hyperplasia. Although glucocorticoid resistance has been associated with glucocorticoid receptor (GR) mutations (encoded by NR3C1 gene), only 23 mutations have been reported so far. We have conducted a French National Research Program, referred to as M...

ea0032p637 | Male reproduction | ECE2013

KISS1R mutations in normosmic congenital hypogonadotropic hypogonadism: clinical evaluation of two families and molecular characterization of a novel mutation

Brioude Frederic , Bouligand Jerome , Francou Bruno , Fagart Jerome , Roussel Ronan , Viengchareun Say , Combettes Laurent , Brailly-Tabard Sylvie , Lombes Marc , Young Jacques , Guiochon-Mantel Anne

Context: KISS1R mutations have been implicated in patients with normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110).Objective: To describe in detail nCHH patients with biallelic KISS1R mutations belonging to two unrelated families, and to functionally characterize a novel KISS1R mutation.Results: The p.Tyr313His original mutant was found in the homozygous state in three affected kindr...

ea0032p649 | Male reproduction | ECE2013

Characterization of R31C GNRH1 mutation in congenital hypogonadotropic hypogonadism

Maione Luigi , Albarel Frederique , Bouchard Philippe , Gallant Megan , Flanagan Colleen A , Bobe Regis , Cohen-Tannoudji Joelle , Pivonello Rosario , Colao Annamaria , Brue Thierry , Lombes Marc , Millar Robert P , Young Jacques , Guiochon-Mantel Anne , Bouligand Jerome

Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare reproductive disease leading to lack of puberty and infertility. Loss-of-function mutations of GNRH1 gene are a very rare cause of autosomal recessive nCHH. R31C GNRH1 is the only missense mutation that affects the conserved GnRH decapeptide sequence. This mutation was identified in a CpG islet in nine nCHH subjects from four unrelated families, giving evidence for a putative ‘hot spot&#...

ea0081oc2.3 | Oral Communications 2: Adrenal and Cardiovascular Endocrinology 1 | ECE2022

Loss of lysine demethylase KDM1A in GIP-dependent bilateral macronodular adrenal hyperplasia with Cushing’s syndrome

Chasseloup Fanny , Bourdeau Isabelle , Tabarin Antoine , Regazzo Daniela , Dumontet Charles , Ladurelle Nataly , Tosca Lucie , Amazit Larbi , Proust Alexis , Scharfmann Raphael , Fiore Frederic , Tsagarakis Stylianos , Vassiliadi Dimitra , Maiter Dominique , Young Jacques , Lecoq Anne-Lise , Demeocq Vianney , Salenave Sylvie , Lefebvre Herve , Cloix Lucie , Emy Philippe , Desailloud Rachel , Vezzosi Delphine , Scaroni Carla , Barbot Mattia , de Herder Wouter , Pattou Francois , Tetreault Martine , Corbeil Gilles , Dupeux Margot , Lambert Benoit , Tachdjian Gerard , Guiochon-Mantel Anne , Beau Isabelle , Chanson Philippe , Viengchareun Say , Lacroix Andre , Bouligand Jerome , Kamenicky Peter

Context: Primary bilateral macronodular adrenal hyperplasia (PBMAH) with glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing’s syndrome is caused by ectopic expression of GIP receptor in the adrenal tissue. The bilateral nature of this adrenal disease suggests germline genetic predisposition. We aimed to identify the molecular driver event responsible for ectopic GIP receptor expression in PBMAH.Methods: We conducted an internationa...