hrp0089p1-p180 | Growth & Syndromes P1 | ESPE2018

Silver Russell and Beckwith-Wiedemann Syndromes: Mosaic Distribution of Epigenetic Anomalies

Pham Aurelie , Giabicani Eloise , Steunou Virginie , Netchine Irene , Brioude Frederic

Background: Genomic imprinting is an epigenetic mechanism referring to the monoallelic silencing of genes according to their parental origin. Human chromosome 11p15.5 encompasses two imprinted domains (ICR1 and ICR2) playing an important role in controlling fetal and postnatal growth. Genetic (uniparental disomy or gain/loss of function mutations) or epigenetic alterations at the 11p15.5 imprinted region (loss or gain of DNA methylation) are associated with two clinical disord...

hrp0092fc12.1 | Growth and Syndromes (to include Turner Syndrome) | ESPE2019

Increasing Knowledge in IGF1R Defects: Lessons from 20 New Patients

Giabicani Eloïse , Willems Marjorie , Steunou Virginie , Chantot-Bastaraud Sandra , Rossignol Sylvie , Le Bouc Yves , Netchine Irène , Brioude Frédéric

Background: IGF1R is a keystone of foetal growth regulation by mediating the effects of both IGF-I and IGF-II. Recently the first clinical cohort of patients carrying an IGF1R defect has been reported from which a clinical score was established for diagnosis. Since no external validation of this score is available we assessed it in a large cohort of patients with identified IGF1R defects. Furthermore we aim at setting-up a functional test to ...

hrp0092rfc8.2 | Pituitary, Neuroendocrinology and Puberty Session 1 | ESPE2019

Investigation of Imprinting Alterations in MKRN3 and DLK1 in a Cohort of Girls with Central Precocious Puberty Through Specific DNA Methylation Analysis

Canton Ana , Steunou Virginie , Brito Vinicius , Laure Sobrier Marie , Montenegro Luciana , Bessa Danielle , Mendonca Berenice B , Netchine Irène , Latronico Ana Claudia

Background: Loss of imprinting has been implicated in the pathogenesis of several human diseases. Monogenic causes of central precocious puberty (CPP) were identified in families with loss-of-function mutations in two paternally expressed imprinted genes: Makorin zinc finger 3 (MKRN3) and Delta-like 1 homolog (DLK1). The role of imprinting defects in CPP has not been described so far.Objective: To inves...

hrp0086p1-p802 | Syndromes: Mechanisms and Management P1 | ESPE2016

Cognitive Evaluation in Silver Russell Children

Patti Giuseppa , Malainho Virginie Coutinho , Dellatolas Georges , Dubern Beatrice , Doummar Diane , Netchine Irene

Background: Silver-Russell syndrome (SRS) is a heterogeneous syndrome characterized by severe intrauterine and postnatal growth retardation and typical dysmorphic features. The major abnormality is the hypomethylation of paternal allele of 11p15 imprinting centre region 1. In 10% of cases a maternal uniparental disomy of chromosome 7 (UPD7) can be detected. Speech delay and learning difficulties have been reported in these patients.Objective and hypothes...

hrp0082fc8.5 | Fat Metabolism | ESPE2014

Putative Gain-of-Function in Rats Carrying the Ghsr Q343X Mutation

Zizzari Philippe , Chebani Yacine , Chettab Khadidja , Pastor Marie , Korostelev Marie , Epelbaum Jacques , Tolle Virginie , Pantel Jacques

Background: The deciphering of the physiological importance of the GH secretagogue receptor (Ghsr), a G protein-coupled receptor (GPCR) depicted as the sole receptor of the pleiotropic hormone ghrelin, was initially compromised by the modest phenotype observed in Ghsr−/− animals. This lack of a robust response to total loss of Ghsr may result from developmental compensatory signals. Still, the description of rare mutations in the GHSR p...

hrp0082fc10.3 | Programming & Early Endocrinology | ESPE2014

Genetic and Epigenetic Defects at the GNAS Locus Lead to Opposite Patterns of Fetal and Postnatal Growth

Grybek Virginie , Maupetit-Mehouas Stephanie , Hogler Wolfgang , Juppner Harald , Silve Caroline , Linglart Agnes

Background: Pseudohypoparathyroidism (PHP) is characterized by proximal tubular resistance to PTH and, in some disease variants, by Albright osteodystrophy. PHP is caused either by mutations in those regions of GNAS encoding Gsα (PHP1A and PseudoPHP) or by GNAS methylation defects (autosomal dominant (AD) and sporadic (spor) PHP1B). Phenotypic differences in fetal growth, post-natal growth and metabolism are observed in the different PHP types.<p cla...

hrp0086rfc2.8 | Bone &amp; Mineral Metabolism | ESPE2016

Final Heights and BMI in Patients Affected with Different Types of Pseudohypoparathyroidism

Hanna Patrick , Mantovani Giovanna , Grybek Virginie , Juppner Harald , Brehin Anne-Claire , Kottler Marie-Laure , Rothenbuhler Anya , Linglart Agnes

Background: Pseudohypoparathyroidism type 1A (PHP1A) and PseudoPHP are caused respectively by maternal and paternal mutations involving those GNAS exons that encode the alpha-subunit of the stimulatory G protein (Gsα). Common to different forms of PHP1B is a loss-of-methylation (LOM) at one or several maternal GNAS exons, which likely reduces Gsα expression in certain tissues. In most autosomal dominant PHP1B variants (AD-PHP1B), LOM is restricted t...

hrp0082p1-d3-86 | Diabetes (2) | ESPE2014

Implementation of Effective Transition from Paediatric to Adult Diabetes Care with an Outpatient Transition Nurse

Elowe-Gruau Eglantine , Aquarone Marie-Paule , Schluter Virginie , Stoppa-Vaucher Sophie , Phan-Hug Franziska , Dwyer Andrew , Pitteloud Nelly , Hauschild Michael

Background: Diabetes mellitus (DM) is a chronic metabolic disorder requiring daily care to prevent both acute and chronic complications. Intensive support to facilitate coping and self-care skills is advocated. Healthcare providers are challenged to manage the transition of adolescents from paediatric to adult diabetes services.Objective and hypotheses: While centres providing structured integrated paediatric and adult care seem optimal, many patients op...

hrp0086fc5.3 | Management of Disorders of Insulin Secretion | ESPE2016

Glibentek, a New Suspension of Glibenclamide for Patients with Neonatal Diabetes, is as Effective and more Convenient than Crushed Tablets

Beltrand Jacques , Godot Cecile , Busiah Kanetee , Djerada Zoubir , Baron Sabine , Tallec Claire Le , Tessier Raphael , Ribault Virginie , Cartigny Maryse , Bruel Henri , Gozalo Claire , Treluyer Jean-Marc , Elie Caroline , Polak Michel

Background: Glibenclamide has proven to be efficient for patients with neonatal diabetes owing to potassium channel mutations. Anyway its pharmaceutical form is not suitable for young children or infants. The tablets dosage is too high for most infants and must be crushed and diluted before administration. We developed a suspension of glibenclamide (EMA Orphean drug designation january 2016) fitting recommendations of drug administration to allow a precise dosage and designed ...

hrp0086fc2.2 | Bone &amp; Mineral Metabolism | ESPE2016

From Pseudohypoparathyroidism to Inactivating PTH/PTHrP Signaling Disorder (iPPSD), a Novel Classification Proposed by the European EuroPHP-Network

Thiele Susanne , Mantovani Giovanna , Barlier Anne , Bordogna Paola , Elli Francesca M , Freson Kathleen , Garin Intza , Grybek Virginie , Hanna Patrick , Izzi Benedetta , Hiort Olaf , Lecumberri Beatriz , Pereda Arrate , de Sanctis Luisa , Silve Caroline , Turan Serap , Usardi Alessia , Saraff Vrinda , de Nanclares Guiomar Perez , Linglart Agnes

Background: Disorders related to an impairment in parathyroid hormone (PTH) signaling pathway are historically classified under the term pseudohypoparathyroidism (PHP), that now encompasses rare, related but highly heterogeneous diseases with demonstrated (epi)genetic causes. The actual classification is based on the presence or absence of specific clinical and biochemical signs together with an in vivo response to exogenous PTH and an in vitro assay of Gs&#9...