PRKACA constitutional duplication: a specific cause of primary pigmented nodular adrenocortical disease
Authors' conclusion
PRKACAdup causes PPNAD but no other forms of BNAD, so these should be sought in the absence of pathogenic PRKAR1A variants.
Study context
- Population
- Index cases with bilateral nodular adrenocortical disease (BNAD): 693 bilateral macronodular hyperplasia and 88 primary pigmented nodular adrenocortical disease (PPNAD), 2020–2024; plus screened relatives
- Participants
- 781 index cases
- Outcome
- Phenotype in carriers of constitutional PRKACA duplication (PRKACAdup)
Methodological detailssystematic screening, next-generation sequencing panel or whole-genome sequencing (WGS), Hi-C chromatin conformation analysis
- Systematic screening
- Next-generation sequencing panel or WGS
- Hi-C chromatin conformation analysis
Main finding
As reported in the abstract
PRKACAdup identified in index cases
8 of 781
PRKACAdup identified in screened relatives
8 of 12
Other Carney complex manifestations (limited to lentiginosis and benign gonadal tumors) in patients with PRKACAdup
8 of the 16
Further findings
WGS in index cases with PPNAD
- No other genetic alterations in disease-associated genes within the duplicated region, nor other adrenal-related alterations (WGS in 4 index cases (IC))
Immunohistochemistry
- PRKACA/PRKAR1A immunohistochemistry facilitated differentiation of the responsible genetic alteration
Chromatin conformation (Hi-C, 3 tumors)
- PRKACAdup generated topologically associated neo-domains in tumor Hi-C maps vs controls
Original publication
PRKACA constitutional duplication: a specific cause of primary pigmented nodular adrenocortical disease. Eur J Endocrinol. Published 16 December 2025. doi:10.
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