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Rhayem, Y.* ; Gustavo Perez-Rivas, L.* ; Dietz, A.* ; Bathon, K.* ; Gebhard, C.* ; Riester, A.* ; Mauracher, B.* ; Gomez-Sanchez, C.* ; Eisenhofer, G.* ; Schwarzmayr, T. ; Calebiro, D.* ; Strom, T.M. ; Reincke, M.* ; Beuschlein, F.*

PRKACA somatic mutations are rare findings in aldosterone-producing adenomas.

J. Clin. Endocrinol. Metab. 101, 3010-3017 (2016)
Verlagsversion Anhang DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
CONTEXT: Somatic mutations have been found causative for endocrine autonomy in aldosterone-producing adenomas (APAs). While mutations of PRKACA (catalytic subunit of protein kinase A) have been identified in cortisol-producing adenomas (CPAs), the presence of PRKACA variants in APAs is unknown, especially in those that display co-secretion of cortisol. OBJECTIVE: To investigate PRKACA somatic variants identified in APA cases. DESIGN: Identification of PRKACA somatic variants in APAs by whole-exome sequencing followed by in vitro analysis of the enzymatic activity of PRKACA variants and functional characterization by double immunofluorescence of CYP11B2 and CYP11B1 expression in the corresponding tumor tissues. SETTING AND PATIENTS: APA tissues were collected from 122 patients who underwent unilateral adrenalectomy for PA between 2005 and 2015 at a single institution. RESULTS: PRKACA somatic mutations were identified in two APA cases (1.6%). One APA carried a newly identified p.His88Asp variant while in a second case a p.Leu206Arg mutation was found, previously described only in CPA with overt Cushing|Aas syndrome. Functional analysis showed that the p.His88Asp variant was not associated with gain of function. While CYP11B2 was strongly expressed in the p.His88Asp mutated APA, the p.Leu206Arg carrying APA predominantly expressed CYP11B1. Accordingly, biochemical Cushing's syndrome was present only in the patient with the p.Leu206Arg mutation. Following adrenalectomy, both patients improved with a reduced number of antihypertensive medications and normalized potassium levels. CONCLUSIONS: We describe for the first time PRKACA mutations as rare findings associated with unilateral PA. As cortisol co-secretion occurs in a sub-group of APAs, other molecular mechanisms are likely to exist.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Dependent Protein-kinase; Pka Catalytic Subunit; Cushings-syndrome; Regulatory Subunit; Channel Mutations; Cortisol; Hypertension; Phenotypes; Diagnosis; Underlie
ISSN (print) / ISBN 0021-972X
e-ISSN 1945-7197
Zeitschrift Journal of Clinical Endocrinology & Metabolism, The
Quellenangaben Band: 101, Heft: 8, Seiten: 3010-3017 Artikelnummer: , Supplement: ,
Verlag Endocrine Society
Verlagsort Bethesda, Md.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)