Clinical phenotypes and molecular genetic mechanisms of Carney complex.
Carney complex is a familial multiple neoplasia disorder with characteristic features such as cardiac and cutaneous myxomas and spotty pigmentation of the skin. Clinical genetic analyses have shown that Carney complex is transmitted in an autosomal dominant way and can present with a wide array of other tumours, such as psammomatous melanotic schwannoma, testicular Sertoli-cell tumours, and pituitary adenomas. Molecular genetic studies show that mutations in the PRKAR1A gene, encoding the R1alpha regulatory subunit of cyclic-AMP-dependent protein kinase A, are the cause of Carney complex in most patients. Investigation of genetically engineered animal models confirms the role of PRKAR1A as a tumour suppressor and has begun to elaborate mechanisms underlying tumorigenesis in this disorder. Further genetic studies in human beings have highlighted novel variant phenotypes, such as congenital contractures, which are potentially associated with Carney complex, and have identified alternative genetic pathways to cardiac tumorigenesis, including mutation of the MYH8 gene that encodes perinatal myosin.
Wilkes
David
D
Molecular Cardiology Laboratory, Greenberg Division of Cardiology, Department of Medicine, Weill Medical College of Cornell University, 525 E. 68th Street, New York, NY 10021, USA.
McDermott
Deborah A
DA
Basson
Craig T
CT
D000818:Animals; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D017868:Cyclic AMP-Dependent Protein Kinases; D005838:Genotype; D006338:Heart Neoplasms / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009232:Myxoma / Q000235:genetics*; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D010641:Phenotype; D010859:Pigmentation Disorders / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics
D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; C517835:Prkar1a protein, mouse; D011506:Proteins; D017868:Cyclic AMP-Dependent Protein Kinases