Carney complex: the first 20 years.
OBJECTIVE
The purpose of this review is to comment on the current findings on Carney complex, a dominantly inherited disease and a unique multiple endocrine neoplasia syndrome.


RESULTS
Sequencing of the PRKAR1A gene in more than 150 kindreds has revealed a number of pathogenic mutations; in more than 90% of the cases, the sequence change was predicted to lead to a premature stop codon and, thus, mutant mRNAs were subject to nonsense-mediated mRNA decay. In Carney complex syndrome cells carrying these mutations, protein kinase A activity is irregularly stimulated by cAMP. Mutations that did not lead to a premature stop codon have also been described; these were also associated with abnormal protein kinase A activity. Animal models of the disease have been recently developed; they reproduced some of the stigmata of Carney complex syndrome but not all. Genetic testing of patients' family members has been introduced in recent years, leading to early detection and a better overall prognosis.


CONCLUSIONS
New treatments have yet to be applied; the elucidation of the molecular pathways regulated by PRKAR1A holds the promise of leading to molecularly designed therapies.
Boikos
Sosipatros A
SA
Section on Endocrinology & Genetics (SEGEN), Developmental Endocrinology Branch (DEB), National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland 20892, USA.
Stratakis
Constantine A
CA
D000172:Acromegaly / Q000473:pathology; D000312:Adrenal Hyperplasia, Congenital / Q000473:pathology*; D003480:Cushing Syndrome / Q000473:pathology*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D006801:Humans; D009377:Multiple Endocrine Neoplasia / Q000473:pathology*; D009154:Mutation; D009232:Myxoma / Q000473:pathology*; D010859:Pigmentation Disorders / Q000235:genetics / Q000473:pathology; D010911:Pituitary Neoplasms / Q000473:pathology*
D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; D017868:Cyclic AMP-Dependent Protein Kinases