hrp0086fc2.1 | Bone & Mineral Metabolism | ESPE2016

Characterization of GNAS miRNAs Targets: Trying to Better Understand the Pathophysiology of Pseudohypoparathyroidism 1B (PHP1B)

Hanna Patrick , Netchine Irene , Le Stunff Catherine , Linglart Agnes

Background: Patients affected with PHP1B are characterized by resistance to PTH which binds to the PTH receptor and activate the cAMP/Gsa signaling pathway. Gsa is encoded by GNAS, a locus subjected to genomic imprinting. PHP1B patients present with abnormal methylation at the maternal A/B promoter and, in some cases, at the other promoters (XLas, GNAS-AS1 and NESP55) of the GNAS locus, likely leading to a decreased express...

hrp0086fc14.2 | Growth : Mechanisms | ESPE2016

CG Methylation at the IGF1 P2 Promoter is a Major Epigenetic Determinant of Postnatal, Not Foetal Growth

Ouni Myriam , Le Stunff Catherine , Castell Anne Laure , Bougneres Pierre

Background: The height of children has a Gaussian distribution. Genetics explain an important part of individual variability, but no single genomic variant accounts for more than 0.3% of height variance. At the interface of genetics and environment, epigenetics is expected to contribute to phenotypic variability. IGF1 is an attractive locus to test this hypothesis.Objectives: To quantify the effect of CG methylation of IGF1 promoters on height.<p cla...

hrp0092rfc15.1 | Late Breaking Abstracts | ESPE2019

Preclinical Studies of Acrodysostosis Gene AAV Therapy in a Knock-In R368X PRKAR1A Mouse Model

Le Stunff Catherine , Gunes Yasemin , Mille Clémence , Bougnères Pierre

The use of recombinant adeno-associated viruses (rAAV) as safe vectors have allowed hundreds of gene therapy attempts to treat monogenic diseases not including bone genetic diseases (Gao G, Nat Rev Drug Dis 2019). To our knowledge, there has been few attempts to apply gene therapy to monogenic bone diseases, largely because most skeletal malformations are being developed during fetal life. Patients affected with acrodysostosis are known to aggravate their skeletal malformation...

hrp0086p1-p98 | Bone &amp; Mineral Metabolism P1 | ESPE2016

Knock in of the Recurrent R368X Mutation of PRKAR1A that Represses cAMP-dependent Protein Kinase A Activation: A Model of Acrodysostosis Type 1?

Le Stunff Catherine , Tilotta Francoise , Sadoine Jeremy , Le Denmat Dominique , Clauser Eric , Bougneres Pierre , Chaussain Catherine , Silve Caroline

Background: In humans, activating mutations in the PRKAR1A gene cause acrodysostosis1 (ACRDYS1). Two striking features of this rare developmental and skeletal disorder are renal resistance to PTH and chondrodysplasia resulting from the constitutive inhibition of PTHR1/Gsa/AC/cAMP/PKA signaling caused by the PRKAR1A mutations.Objective and hypotheses: Document the consequences of the germline expression of a PRKAR1A mutation causing a dominant repression ...