ESPEYB15 8 Adrenals New Genes (1 abstracts)
8.13 Activating PRKACB somatic mutation in cortisol-producing adenomas
Espiard S , Knape MJ , Bathon K , Assié G , Rizk-Rabin M , Faillot S , Luscap-Rondof W , Abid D , Guignat L , Calebiro D , Herberg FW , Stratakis CA & Bertherat J
Cochin Institute, Paris Descartes University, CNRS (UMR 8104)/Inserm (U1016), Paris, France
To read the full abstract: JCI Insight. 2018; 3(8). pii: 98296
Adrenocortical cells depend on cAMP/PKA signaling for growth and steroidogenesis. Several adrenal disorders manifesting with Cushing syndrome (CS) are due to activation of the PKA pathway, including Carney complex and primary pigmented nodular adrenal disease (due to germline mutations of PRKA1RA), McCune-Albright syndrome (due to mosaic mutations of GNAS (Gsα subunit)), as well as other nodular adrenal disorders caused by germline or somatic mutations of phosphodiesterases 11A or 8B. Cortisol-producing adenomas (CPA) are the most common cause of adrenal CS. They are also due to activating mutations in the PKA signaling pathway. Recently, somatic mutations of protein kinase cAMP-activated catalytic subunit α (PRKACA) have been found in CPA leading to loss of interaction with R subunits and thus an increase in total PKA activity. In this article, a somatic mutation (S54L) in the catalytic subunit β (PRKACB) has been found in a CPA leading to severe CS likely due to disruption of stability of type I PKA holoenzyme. Although found only in one case of CPA so far, disease-causality is likely as previous studies have already established a possible role for PRKACB in tumorigenesis, and a triplication of the gene has been recently reported in a patient with Carney complex (24). Therefore, PRKACB should be regarded as a novel candidate gene associated with endocrine active tumors.
24. Forlino A, Vetro A, Garavelli L, Ciccone R, London E, Stratakis CA, Zuffardi O. PRKACB and Carney complex. N Engl J Med 2014; 370:1065-1067.
Volume 15
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more