Introduction: Pigmented micronodular adrenal dysplasia (PMNAD) is an infrequent cause of Cushing syndrome ACTH-independent, and can form a part of Carney syndrome (CS). In both, regulatory subunit mutations of the protein kinase A (PRKAR1A) have been demonstrated, but without apparent genotype-phenotype correlation.
Objective: To demonstrate the mutation of PRKAR1A and its functional and clinical expression in a family affected with PMNAD.
Material and method: The index case and nine members of the family at risk were valued to demonstrate mutation of the gene PRKAR1A after diagnosed with PMNAD. DNA was extracted from the index patient and nine family members, primarily to study the segregation and linkage to locus of the PRKRA1A gene. Analysis of microsatellites was done by PCR using 32p-dCTP and autoradiograph of alleles after electrophoresis in acrylamide gel. Afterwards, the sequence was determined. Basal and post dexamethasone plasmatic and urinary cortisol and ACTH were valued.
Results: We describe a deletion of six pared sequence bases of the polypyrimidne tract [exon 7 IVS del (−7→−2)] of PRKRA1A gene in the index case and in four family members, three of them revealing PNMAD. In the remaining two family members (father and aunt of index patient), hypercorticism was not seen, although the father showed paradoxical response to dexamethasone on one occasion. Clinical manifestations of CS were not described. The other family members did not show PRKAR1A mutation.
Conclusions: A small intronic deletion of PRKAR1A gene could cause PMNAD, with a varying grade of penetration and clinical expression. This shows us the first genetic defect of PRKAR1A gene, which is associated to a specific phenotype.