Unknown

Dataset Information

0

Genomic and sequence variants of protein kinase A regulatory subunit type 1? (PRKAR1B) in patients with adrenocortical disease and Cushing syndrome.


ABSTRACT:

Purpose

Protein kinase A (PKA) subunit defects (in PRKAR1A and PRKACA) are known to contribute to adrenal tumor pathogenesis. We studied the PRKAR1B gene for any genetic changes in bilateral adrenocortical hyperplasia (BAH) and cortisol-producing adrenal adenomas (CPA).

Methods

Exome sequencing and PRKAR1B copy-number variant (CNV) analysis were performed in 74 patients with BAH and 21 with CPA. PKA activity was studied in tumors with defects; sequence variants were investigated in vitro.

Results

Three PRKAR1B germline variants (p.I40V, p.A67V, p.A300T) were identified among 74 patients with BAH. PRKAR1B copy-number gains (CNG) were found in 3 of 21 CPAs, one in a tumor carrying a somatic PRKACA "hotspot" pathogenic variant p.L206R. CPAs bearing PRKAR1B CNGs showed higher PRKAR1B messenger RNA (mRNA) levels and reduced PKA activity. Baseline PKA activity was also decreased for p.A67V and p.A300T in vitro, and mutant PRKAR1? bound PRKAC? in fluorescence resonance energy transfer (FRET) recordings of cotransfected HEK293 cells stronger than normal.

Conclusion

PRKAR1B is yet another PKA subunit that may potentially contribute to adrenal tumor formation. Its involvement in adrenocortical disease may be different from that of other subunits, because PRKAR1B variants and PRKAR1B CNGs were associated with decreased (rather than increased) overall PKA activity in vitro.

SUBMITTER: Drougat L 

PROVIDER: S-EPMC7796991 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Genomic and sequence variants of protein kinase A regulatory subunit type 1β (PRKAR1B) in patients with adrenocortical disease and Cushing syndrome.

Drougat Ludivine L   Settas Nikolaos N   Ronchi Cristina L CL   Bathon Kerstin K   Calebiro Davide D   Maria Andrea Gutierrez AG   Haydar Sara S   Voutetakis Antonios A   London Edra E   Faucz Fabio R FR   Stratakis Constantine A CA  

Genetics in medicine : official journal of the American College of Medical Genetics 20200908 1


<h4>Purpose</h4>Protein kinase A (PKA) subunit defects (in PRKAR1A and PRKACA) are known to contribute to adrenal tumor pathogenesis. We studied the PRKAR1B gene for any genetic changes in bilateral adrenocortical hyperplasia (BAH) and cortisol-producing adrenal adenomas (CPA).<h4>Methods</h4>Exome sequencing and PRKAR1B copy-number variant (CNV) analysis were performed in 74 patients with BAH and 21 with CPA. PKA activity was studied in tumors with defects; sequence variants were investigated i  ...[more]

Similar Datasets

| S-EPMC4042182 | biostudies-other
| S-EPMC2853983 | biostudies-literature
| S-EPMC2845687 | biostudies-literature
| S-EPMC7566855 | biostudies-literature
| S-EPMC2859386 | biostudies-literature
| S-EPMC9170649 | biostudies-literature
| S-EPMC7941762 | biostudies-literature
| S-EPMC8728871 | biostudies-literature
| S-EPMC126049 | biostudies-literature
| S-EPMC5437744 | biostudies-literature