Pseudohypoparathyroidism: inheritance of deficient receptor-cyclase coupling activity.
Pseudohypoparathyroidism, type I (PHP-I) is an inherited disorder of primary resistance to multiple hormones that work by stimulating adenylate cyclase. In an attempt to clarify the mode of inheritance of PHP-I, we measured the activity of the N protein, a receptor-cyclase coupling component, in erythrocyte membranes. Erythrocyte N-protein activity was reduced by approximately 50% in erythrocytes of 15 PHP-I patients and was normal in 19 of their clinically normal first degree relatives. Reduced N-protein activity and the PHP-I phenotype in these families exhibited both dominant and recessive patterns of inheritance. This suggests that at least two distinct genetic loci are involved in inheritance of N-protein deficiency. In two additional families, dominant inheritance of the PHP-I phenotype was associated with normal activities of erythrocyte N protein. Thus, it appears that mutation of at least one additional genetic locus, not involving the N protein, can produce PHP-I.
D000262:Adenylyl Cyclases / Q000172:deficiency* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000097:blood; D002675:Child, Preschool; D000242:Cyclic AMP / Q000652:urine; D004912:Erythrocytes / Q000032:analysis; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010375:Pedigree; D011547:Pseudohypoparathyroidism / Q000235:genetics*; D012016:Reference Values
D008565:Membrane Proteins; D010281:Parathyroid Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium