One of the putative CNC genes located on 17q22-24, (PRKAR1A), has been identified to encode the regulatory subunit (R1A) of protein kinase A. Heterozygous inactivating mutations of PRKAR1A were reported initially in 45 to 65 % of CNC index cases, and may be present in about 80 % of the CNC families presenting mainly with Cushing's syndrome. Here, PRKAR1A is linked to Cushing syndrome due to macronodular adrenal hyperplasia.