Some patients with PHP-I display distinctive physical features collectively termed Albright’s hereditary osteodystrophy [119]. These features include obesity, short stature, ectopic ossification, brachydactyly, and mild mental retardation, although there is significant patient-to-patient variation in the range and severity of these features. The presence of both PTH-resistance and AHO defines patients with PHP type-Ia. Gsα mRNA and protein levels are reduced to half in easily accessible tissues from these patients [126-128]. This defect results from heterozygous inactivating mutations within one of the thirteen Gsα coding GNAS exons [129, 130]. Scattered throughout the gene, various different types of mutations, such as insertions, deletions, and missense and nonsense changes, have been identified, which is consistent with their inactivating nature. An extensive list of the mutations associated with this disorder can be found under OMIM entry #139320 at http://www.ncbi.nlm.nih.gov.
