Recurrent somatic mutations underlie corticotropin-independent Cushing's syndrome.

[cushing syndrome]

Cushing 's syndrome is caused by excess cortisol production from the adrenocortical gland . In corticotropin-independent Cushing 's syndrome , the excess cortisol production is primarily attributed to an adrenocortical adenoma , in which the underlying molecular pathogenesis has been poorly understood . We report a hotspot mutation (L 206 R ) in PRKACA , which encodes the catalytic subunit of cyclic adenosine monophosphate (cAMP )-dependent protein kinase (PKA ), in more than 50 % of cases with adrenocortical adenomas associated with corticotropin-independent Cushing 's syndrome . The L 206 R PRKACA mutant abolished its binding to the regulatory subunit of PKA (PRKAR 1 A ) that inhibits catalytic activity of PRKACA , leading to constitutive , cAMP-independent PKA activation . These results highlight the major role of cAMP-independent activation of cAMP /PKA signaling by somatic mutations in corticotropin-independent Cushing 's syndrome , providing insights into the diagnosis and therapeutics of this syndrome .

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Diseases presenting "in which the underlying molecular pathogenesis has been poorly understood" symptom

cushing syndrome

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