ESPE Abstracts

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...

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...

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...

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 ...