Some patients with PTH-resistance lack AHO and any additional hormone resistance, defining the typical features of PHP type-Ib (PHP-Ib). Recent studies have demonstrated that some PHP-Ib patients also have mild TSH resistance in addition to PTH resistance [89, 90, 151]. Furthermore, a single study described several patients who showed both the epigenetic defects characteristic of PHP-Ib (see below) and mild features of AHO [152], suggesting more variation in the phenotype. Unlike in PHP-Ia, Gsα activity is typically normal in easily accessible cells from these patients, thus excluding mutations within Gsα coding GNAS exons [131, 153]. Nonetheless, in three related patients with an apparent diagnosis of PHP-Ib an in-frame, tri-nucleotide deletion has been identified within exon 13 [154]. Expressed in HEK293 cells, an embryonic kidney derived cell line, this Gsα mutant was shown to affect the signaling of PTH, but not of TSH, LH, or isoproterenol, thus explaining the isolated PTH resistance. The selective effect of this mutation on PTH signaling, however, could not be verified in a subsequent study [70], and it is possible that the discrepancy between the two
