Genetics of Carney Complex

摘要: Carney complex (CNC) is an autosomal dominant multiple neoplasia and lentiginosis syndrome characterised by spotty skin lesions, cardiac other myxomas different types of endocrine tumours. The PRKAR1A gene, which codes for the regulatory subunit type 1-alpha cyclic adenosine monophosphate (cAMP)-activated protein kinase A, responsible more than two-thirds cases CNC described to date. Currently, 120 disease-causing sequence variants have been reported. Other involved genes adrenal hyperplasias include phosphodiesterases PDE11A PDE8B. Additional are likely be identified that may expand our understanding on pathophysiology cAMP signalling pathway how genetic defects cause its individual components such as tumours. Key Concepts: Inactivating mutations because haploinsufficiency leads uncontrolled PKA activity. The majority (∼80%) causing result in early stop codon generation degradation mutant RNA through nonsense-mediated decay (NMD). Recently, novel described: large gene rearrangements small indels resulting elongated downstream shift codon. The penetrance 95% age 50 years. PDE11A PDE8B contribute phenotype, but they also independently forms hyperplasia, mainly isolated micronodular adrenocortical disease (iMAD). Genotype–phenotype correlation limited, there certain frequently manifestations Cushing syndrome. The use new genomic techniques has led identification related CNC. Keywords: Carney complex; PRKAR1A; mutations; PDE11A; PDE8B; genotype-phenotype correlations