Inactivating Gsα mutations found in PHP-Ia patients are also present in patients who lack hormone resistance but present with AHO features, a condition referred to as pseudopseudohypoparathyroidism (PPHP) [139]. Mutations in patients with PPHP are often identical to those in PHP-Ia patients. In fact, both disorders typically co-exist in the same kindred [129, 140], with the gender of the affected parent determining whether the offspring will have PHP-Ia or PPHP: maternal inheritance leads to PHP-Ia, whereas paternal inheritance leads to PPHP [141, 142]. Thus, hormone resistance (PHP-Ia) is inherited only from female obligate carriers, a mode of inheritance that is consistent with the predominantly maternal expression of Gsα in certain tissues. It is important to note that the repertoire of hormone resistance in PHP-Ia correlates well with the tissues in which maternal, monoallelic Gsα expression takes place, underscoring the significance of Gsα imprinting in the pathogenesis of PHP-Ia.
