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: 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: 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...