Indeed, PHP-Ia and PPHP are caused by inactivating mutations within the GNAS gene, which is located on the long arm of chromosome 20 in humans and contains 13 exons.[8] All exons can be affected by loss-of-function alterations, of which small insertions/deletions and amino acid substitutions are most commonly found.[9] The mutation leads to a dramatic reduction in Gsα expression or activity in certain tissues, thus resulting in abnormal signaling of cAMP-dependent pathways.[10] The mutation is maternally inherited in PHP-Ia while paternally inherited in PPHP.[11]. This evidence concerns the gene GNAS and pseudopseudohypoparathyroidism.