Clinical and molecular genetics of primary pigmented nodular adrenocortical disease.
Carney complex (CNC) is a multiple endocrine neoplasia (MEN) syndrome associated with other, non-endocrine manifestations such as lentigines, cardiac myxomas and schwannomas. Primary pigmented nodular adrenocortical disease (PPNAD), leading to corticotrophin-independent Cushing's syndrome is the most frequent endocrine lesion in CNC. The complex has been mapped to 2p16 and 17q22-24, although additional heterogeneity may exist. The gene coding for the protein kinase A (PKA) type I-a regulatory subunit (RIa), PRKAR1A, had been mapped to 17q. Cloning of the PRKAR1A genomic structure and its sequencing showed mutations in CNC-, CNC with PPNAD- and sporadic PPNAD-patients. In CNC tumors, PKA activity showed increased stimulation by cAMP, whereas PKA activity ratio was decreased, and in CNC tumors, there is LOH of the normal allele, suggesting that normal PRKAR1A may be a tumor suppressor in these tissues. CNC is the first human disease caused by mutations of one of the subunits of the PKA enzyme, a critical component of the cAMP signaling system and a potential participant in many other signaling pathways.
Sandrini
Fabiano
F
Section on Endocrinology & Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892-1862, USA. fsandrini@globo.com
Stratakis
Constantine
C
D000303:Adrenal Cortex Diseases / Q000175:diagnosis* / Q000235:genetics*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases; D006801:Humans; D011506:Proteins / Q000235:genetics
D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; D011506:Proteins; D017868:Cyclic AMP-Dependent Protein Kinases