ABSTRACT
This chapter focuses on the imprinting of the various GNAS1 gene products, the mutational spectrum of the gene having recently been comprehensively reviewed elsewhere. The name of the Boston endocrinologist Fuller Albright is now usually associated with two syndromic endocrine disorders; Albright hereditary osteodystrophy (AHO) and McCune Albright syndrome. Several subtypes of Pseudohypoparathyroidism (PHP) are now defined on the basis of endocrinological parameters. The commonest of these, PHP-Ia, has the clinical features of: short stature with an osteodystrophy affecting particularly the metacarpals and metatarsals; frequently subcutaneous or intracerebral calcification; round facies; and mild mental retardation in some patients. PHP-Ia is characterized by end-organ resistance to the action of various hormones that act as ligands for cell-surface receptors of the seven transmembrane domain class. The recognition that the hormones to which there is end-organ resistance in PHP-Ia are adenylate cyclase-coupled, led to the biochemical demonstration of deficient receptor-cyclase coupling activity in patients' erythrocyte membranes.
