Pseudohypoparathyroidism: inheritance of deficient receptor-cyclase coupling activity.

Abstract

Pseudohypoparathyroidism, type I (PHP-I) is an inherited disorder of primary resistance to multiple hormones that work by stimulating adenylate cyclase. To clarify the mode of inheritance of PHP-I, the activity of the N protein, a receptor-cyclase coupling component, in erythrocyte membranes was measured. Erythrocyte N-protein activity was reduced by .apprxeq. 50% in erythrocytes of 15 PHP-I patients and was normal in 19 of their clinically normal 1st degree relatives. Reduced N-protein activity and the PHP-I phenotype in these families exhibited both dominant and recessive patterns of inheritance. Evidently at least 2 distinct genetic loci are involved in inheritance of N-protein deficiency. In 2 additional families, dominant inheritance of the PHP-I phenotype was associated with normal activities of erythrocyte N protein. Apparently mutation of at least 1 additional genetic locus, not involving the N protein, can produce PHP-I.