hrp0086rfc2.7 | Bone & Mineral Metabolism | ESPE2016

Effect of Paternal Loss-of-Function Mutations of GNAS on Growth During the Childhood: A Role for XL

Tran Lea Chantal , Brehin Anne-Claire , Richard Nicolas , Kottler Marie-Laure

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...

hrp0086rfc10.1 | Perinatal Endocrinology | ESPE2016

Paternal Loss-of-Function Mutations of GNAS and Growth Retardation in a Mice Model: A Specific Placental Transcriptomic Signature?

Tran Lea Chantal , Ballandone Celine , Vaiman Daniel , Barbaux Sandrine , Richard Nicolas , Kottler Marie-Laure

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 ...

hrp0082p1-d3-48 | Bone (1) | ESPE2014

Paternal Isodisomy and Sporadic Pseudohypoparathyroidism I-b

Colson Cindy , Brehin Anne Claire , Abeguile Genevieve , Decamp Matthieu , Richard Nicolas , Kottler Marie-Laure

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...

hrp0086p1-p688 | Endocrinology and Multisystemic Diseases P1 | ESPE2016

Thyrotoxicosis, Nephrogenic Syndrome of Inappropriate Antidiuresis, Tall Stature and Mental Retardation Caused by a Novel GNAS Gain of Function Mutation

Houang Muriel , Kottler Marie-Laure , Bensman Albert , Haymann Jean-Philippe , Richard Nicolas , Dunand Olivier , Bastepe Murate , Silve Caroline , Coudray Nathalie , Netchine Irene , Linglart Agnes

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...