ESPE Abstracts

Background: Heterozygous GNAS inactivating mutations cause pseudohypoparathyroidism type Ia (PHP-Ia) when maternally inherited and pseudopseudohypoparathyroidism (PPHP)/progressive osseous heteroplasia when paternally inherited. Mutations on the paternal, but not the maternal, GNAS allele are associated with intrauterine growth retardation (IUGR). Moreover, birth weights were lower with paternal GNAS mutations affecting exons 2–13 (including XL and Gαs) than with exo...

Background: GNAS gene is a complex imprinted locus, resulting in the expression of at least four transcripts (XL, NESP55, A/B and Gsα) characterized by their specific exon 1 and common exons 2-13. While Gαs is biallelically expressed in most tissues, XL is only expressed from the paternal allele. Maternally inherited, loss-of-function mutations affecting those GNAS exons that ...

Background: Patients affected by pseudohypoparathyroidism type 1b (PHPI-b) develop resistance to PTH leading to hypocalcemia and hyperphosphoremia, which is often associated with resistance to TSH. PHP-Ib is associated with methylation changes at one or several differentially methylated regions (DMRs) within the GNAS complex locus, located at 20q13.2–13.3. This locus gives rise to several different transcripts (NESP55, XL, A/B), with varying patterns of imprinted expressi...

Background: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a very rare clinical condition. Patients suffer from hyponatremia, hypo-osmolality with inappropriately elevated urinary osmolality and undetectable AVP levels. Activating mutations of AVPR2, the vasopressin receptor type 2 (V2R), induce a prolonged signaling of the intracellular cAMP/PKA pathway and cause NSIAD in patients.Objective and hypotheses: To describe a new phenotype in a...