Mutations of the gene encoding the protein kinase A type I-α regulatory subunit in patients with the Carney complex
Abstract
Carney complex (CNC) is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumours and psammomatous melanotic schwannomas. CNC is inherited as an autosomal dominant trait and the genes responsible have been mapped to 2p16 and 17q22-24 (refs 6, 7). Because of its similarities to the McCune-Albright syndrome and other features, such as paradoxical responses to endocrine signals, genes implicated in cyclic nucleotide-dependent signalling have been considered candidates for causing CNC (ref. 10). In CNC families mapping to 17q, we detected loss of heterozygosity (LOH) in the vicinity of the gene (PRKAR1A) encoding protein kinase A regulatory subunit 1-alpha (RIalpha), including a polymorphic site within its 5' region. We subsequently identified three unrelated kindreds with an identical mutation in the coding region of PRKAR1A. Analysis of additional cases revealed the same mutation in a sporadic case of CNC, and different mutations in three other families, including one with isolated inherited cardiac myxomas. Analysis of PKA activity in CNC tumours demonstrated a decreased basal activity, but an increase in cAMP-stimulated activity compared with non-CNC tumours. We conclude that germline mutations in PRKAR1A, an apparent tumour-suppressor gene, are responsible for the CNC phenotype in a subset of patients with this disease.
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Somatic mutations of PRKAR1A have been described in some sporadic adrenocortical tumors.
“Although mutations in this gene were first described in Carney complex (145), somatic mutations of PRKAR1A have been described in some sporadic adrenocortical tumors (146).”
From Adrenal incidentaloma (2020) · cites this paper as [145]
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Self-citation
- Authors
- Kirschner, L. S., Carney, J. A., Pack, S. D., Taymans, S. E., Giatzakis, C., Cho, Y. S., Cho-Chung, Y. S., & Stratakis, C. A.
- Affiliations
- National Institutes of Health (US)
- Mayo Clinic (US)
- Corresponding author
- Stratakis, Constantine A.
- Venue
- Nature Genetics
- Published
- 2000-09
- Volume
- 26
- Issue
- 1
- Pages
- 89-92
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2124127909
- Cited by
- 1,153
- References
- 27
- Citations by year
- 2026: 26 · 2025: 17 · 2024: 32 · 2023: 31 · 2022: 45 · 2021: 51 · 2020: 48 · 2019: 34 · 2018: 46 · 2017: 51 · 2016: 53 · 2015: 50 · 2014: 60 · 2013: 46 · 2012: 46
- FWCI
- 26.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac tumors and thrombi
- Keywords
- Carney complex, PRKAR1A, germline mutations, tumor suppressor, loss of heterozygosity, cardiac myxoma, cAMP signaling, McCune-Albright syndrome, endocrine tumors
- MeSH terms
- Acromegaly, Cyclic AMP, Alleles, Chromatography, High Pressure Liquid, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 2, DNA Mutational Analysis, Endocrine Gland Neoplasms, Exons, Family Health, Female, Genotype, Homozygote, Humans, Introns, Male, Molecular Sequence Data, Mutation, Myxoma, Neoplasms, Neurilemmoma, Nucleic Acid Heteroduplexes, Pedigree, Phenotype, Polymorphism, Genetic, Skin Pigmentation, Blotting, Western, Cyclic AMP-Dependent Protein Kinases, DNA, Complementary, Germ-Line Mutation, Microsatellite Repeats, Loss of Heterozygosity, Expressed Sequence Tags
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