Carney complex is a syndrome characterized by the occurrence of multiple neoplasia. Typical features are pigment spots on the skin and mucous membranes, myxomas of the skin, heart and breast, endocrine tumors and increased endocrine activity.
Carney complex is a genetically heterogenous disease. So far, two chromosomal regions associated with the disease have been mapped. In the region 17q24 there was found the PRKAR1A gene which is mutated in about 50 % of all Carney complex cases. PRKAR1A gene encodes the regulatory subunit cAMP - dependent on protein kynase A which is an important effector molecule in many endocrine signaling pathways.
Another chromosomal region associated with Crney complex is 2p16 but the concrete gene has not been identified yet.
We investigate all ten coding exons of the PRKAR1A gene. We use PCR amplification of the targeted region and direct sequencing.
In approximately 70% of patients with Carney complex is found the inactivating heterozygous mutations tumor suppressor gene PRKAR1A (Bertherat, 2009).
Sequence analysis of the coding exons and exon-intron connections detects approximately 95% of mutations in the gene PRKAR1A listed in a publicly available version of the mutation database HGMD (The Human Gene Mutation Database).
Analytical sensitivity and specificity of the sequencing of 99%.
Mutations deep in the introns and regulatory sequences are not detected. Deletions and duplications are not detected. Rare polymorphisms in the location of primers annealing may cause a diagnostic error.
- Bossis I, Stratakis CA. Minireview: PRKAR1A: normal and abnormal functions. Endocrinology. 2004 Dec;145(12):5452-8.