McGlacken-Byrne, SM;
Abdelmaksoud, A;
Haini, M;
Palm, L;
Ashworth, M;
Li, J;
Wang, W;
... Dattani, MT; + view all
(2022)
Mosaic PRKACA duplication causing a novel and distinct phenotype of early-onset Cushing’s syndrome and acral cutaneous mucinosis.
European Journal of Endocrinology
, 187
(6)
K55-K61.
10.1530/EJE-22-0287.
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Abstract
Genetic alterations within the cAMP/protein kinase A (PKA) pathway result in a spectrum of adrenocortical disorders. Implicated genes include GNAS, PDE8B, PDE11A, PRKAR1A/B, and PRKACA. To date, pathogenic somatic PRKACA variants and germline PRKACA copy number gain have been associated with the development of cortisol-secreting adrenocortical adenomas and bilateral adrenal hyperplasia, respectively. While perturbations within the PRKAR1A gene are known to cause Carney complex, PKRACA mutations are rarely associated with an extra-adrenal phenotype. We describe a mosaic PRKACA duplication in an infant who presented with a Carney-like complex at the age of 3 months with bilateral non-pigmented micronodular adrenal hyperplasia, severe early-onset Cushing’s syndrome, and distinct acral soft tissue overgrowth due to cutaneous mucinosis. This represents a novel manifestation of PRKACA disruption and broadens its extra-adrenal phenotype. It suggests that the Cushing’s syndrome phenotypes arising from somatic and germline PRKACA abnormalities likely exist on a spectrum. We emphasise the importance of ascertaining a genetic diagnosis for PRKACA-mediated disease.
| Type: | Article |
|---|---|
| Title: | Mosaic PRKACA duplication causing a novel and distinct phenotype of early-onset Cushing’s syndrome and acral cutaneous mucinosis |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1530/EJE-22-0287 |
| Publisher version: | https://doi.org/10.1530/EJE-22-0287 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Endocrinology & Metabolism, PROTEIN-KINASE-A, CATALYTIC SUBUNIT, REGULATORY SUBUNIT, SOMATIC MUTATIONS, VARIANTS, GERMLINE, ACTIVATION, MECHANISMS, PATHWAY, DISEASE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10173540 |
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