Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Mutations in the protein kinase A R1α regulatory subunit cause familial cardiac myxomas and Carney complex
Mairead Casey, … , Cynthia C. Morton, Craig T. Basson
Mairead Casey, … , Cynthia C. Morton, Craig T. Basson
Published September 1, 2000
Citation Information: J Clin Invest. 2000;106(5):R31-R38. https://doi.org/10.1172/JCI10841.
View: Text | PDF | Corrigendum
Rapid Publication

Mutations in the protein kinase A R1α regulatory subunit cause familial cardiac myxomas and Carney complex

  • Text
  • PDF
Abstract

Cardiac myxomas are benign mesenchymal tumors that can present as components of the human autosomal dominant disorder Carney complex. Syndromic cardiac myxomas are associated with spotty pigmentation of the skin and endocrinopathy. Our linkage analysis mapped a Carney complex gene defect to chromosome 17q24. We now demonstrate that the PRKAR1α gene encoding the R1α regulatory subunit of cAMP-dependent protein kinase A (PKA) maps to this chromosome 17q24 locus. Furthermore, we show that PRKAR1α frameshift mutations in three unrelated families result in haploinsufficiency of R1α and cause Carney complex. We did not detect any truncated R1α protein encoded by mutant PRKAR1α. Although cardiac tumorigenesis may require a second somatic mutation, DNA and protein analyses of an atrial myxoma resected from a Carney complex patient with a PRKAR1α deletion revealed that the myxoma cells retain both the wild-type and the mutant PRKAR1α alleles and that wild-type R1α protein is stably expressed. However, in this atrial myxoma, we did observe a reversal of the ratio of R1α to R2β regulatory subunit protein, which may contribute to tumorigenesis. Further investigation will elucidate the cell-specific effects of PRKAR1α haploinsufficiency on PKA activity and the role of PKA in cardiac growth and differentiation.

Authors

Mairead Casey, Carl J. Vaughan, Jie He, Cathy J. Hatcher, Jordan M. Winter, Stanislawa Weremowicz, Kate Montgomery, Raju Kucherlapati, Cynthia C. Morton, Craig T. Basson

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2018 2017 2015 2014 2013 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 Total
Citations: 1 1 1 3 5 2 3 1 1 9 3 5 7 4 4 4 5 1 1 3 1 3 68
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (68)

Title and authors Publication Year
Detection of PRKAR1A gene mutations in sporadic cardiac myxomas: a study of 24 cases
Bekers E, van Bladel DA, Berendsen MR, Eijkelenboom A, van Krieken JH, Ooft M, Ruijter E, Verhagen A, Flucke UE, Scheijen B
Virchows Archiv 2025
Protein kinase A and local signaling in cancer
Rosenthal KJ, Gordan JD, Scott JD
The Biochemical journal 2024
Progress in Thyroid Cancer Genomics: A 40-Year Journey
Fagin JA, Nikiforov YE
Thyroid : official journal of the American Thyroid Association 2023
Protein Kinase A Downregulation Delays the Development and Progression of Polycystic Kidney Disease
Wang X, Jiang L, Thao K, Sussman CR, LaBranche T, Palmer M, Harris PC, McKnight GS, Hoeflich KP, Schalm S, Torres VE
Journal of the American Society of Nephrology : JASN 2022
Association between subclinical hyperthyroidism and a PRKAR1A gene variant in Carney complex patients: A case report and systematic review
Wang H, Mao M, Liu D, Duan L
Frontiers in Endocrinology 2022
Treatment of Primary Pigmented Nodular Adrenocortical Disease
Liu X, Zhang S, Guo Y, Gang X, Wang G
Hormone and Metabolic Research 2022
Genes Regulating Spermatogenesis and Sperm Function Associated With Rare Disorders
E Linn, L Ghanem, H Bhakta, C Greer, M Avella
Frontiers in Cell and Developmental Biology 2021
Bilateral Adrenal Hyperplasia: Pathogenesis and Treatment
B Chevalier, MC Vantyghem, S Espiard
Biomedicines 2021
Mitochondrial A‐kinase anchoring proteins in cardiac ventricular myocytes
RT Sherpa, C Fiore, KS Moshal, A Wadsworth, MW Rudokas, SR Agarwal, RD Harvey
Physiological Reports 2021
A new classification of cardio-oncology syndromes
RA de Boer, JP Aboumsallem, V Bracun, D Leedy, R Cheng, S Patel, D Rayan, S Zaharova, J Rymer, JM Kwan, J Levenson, C Ronco, P Thavendiranathan, SA Brown
Cardio-Oncology 2021
PRKAR1A and Thyroid Tumors
G Pitsava, CA Stratakis, FR Faucz
Cancers 2021
PRKAR1A deficiency impedes hypertrophy and reduces heart size
Y Liu, P Xia, J Chen, WP Bandettini, LS Kirschner, CA Stratakis, Z Cheng
Physiological Reports 2020
Palatal Soft Tissue Myxoma in a Patient with Carney Complex
BA Mariz, EM Tager, CC Fernandez, OP de Almeida, R Carlos
Head and Neck Pathology 2020
A novel splice site mutation of the PRKAR1A gene, C.440+5 G>C, in a Chinese family with Carney complex
J Fu, F Lai, Y Chen, X Wan, G Wei, Y Li, H Xiao, X Cao
Journal of Endocrinological Investigation 2018
Cytologic diagnosis of unusual, large multiple cutaneous myxomas in a case of Carney complex
M Karegar, M Sarwate, K Kothari, A Rojekar, L Naik
Journal of laboratory physicians 2018
Detection of new potentially pathogenic mutations in two patients with primary pigmented nodular adrenocortical disease (PPNAD) — case reports with literature review
K Pasternak-Pietrzak, CA Stratakis, E Moszczyńska, A Lecka-Ambroziak, M Staniszewski, U Wątrobińska, C Lyssikatos, M Prokop-Piotrkowska, W Grajkowska, M Pronicki, M Szalecki
2018
Recurrent somatic mutations of PRKAR1A in isolated cardiac myxoma
J He, M Sun, E Li, Y Hou, MJ Shepard, D Chen, K Pacak, C Wang, L Guo, Z Zhuang, Y Liu
Oncotarget 2017
The pleiotropic role of exchange protein directly activated by cAMP 1 (EPAC1) in cancer: implications for therapeutic intervention
M Almahariq, FC Mei, X Cheng
Acta Biochimica et Biophysica Sinica 2015
Loss of Prkar1a leads to Bcl-2 family protein induction and cachexia in mice
L Gangoda, M Doerflinger, R Srivastava, N Narayan, LE Edgington, J Orian, C Hawkins, LA O'Reilly, H Gu, M Bogyo, P Ekert, A Strasser, H Puthalakath
Cell Death and Differentiation 2014
Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors
G Goh, UI Scholl, JM Healy, M Choi, ML Prasad, C Nelson-Williams, JW Kuntsman, R Korah, AC Suttorp, D Dietrich, M Haase, HS Willenberg, P Stålberg, P Hellman, G Åkerström, P Björklund, T Carling, RP Lifton
Nature Genetics 2014
mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD)
C Joussineau, I Sahut-Barnola, F Tissier, T Dumontet, C Drelon, M Batisse-Lignier, I Tauveron, JC Pointud, AM Lefrancois-Martinez, CA Stratakis, J Bertherat, P Val, A Martinez
Human Molecular Genetics 2014
Insights from systems pharmacology into cardiovascular drug discovery and therapy
P Li, Y Fu, J Ru, C Huang, J Du, C Zheng, X Chen, P Li, A Lu, L Yang, Y Wang
BMC Systems Biology 2014
D-AKAP2:PKA RII:PDZK1 ternary complex structure: Insights from the nucleation of a polyvalent scaffold: D-AKAP2 Mediated Anchoring of PDZK1 and PKA RII Isoform
GN Sarma, IS Moody, R Ilouz, RH Phan, B Sankaran, RA Hall, SS Taylor
Protein Science 2014
Neutron Diffraction Reveals Hydrogen Bonds Critical for cGMP-Selective Activation: Insights for cGMP-Dependent Protein Kinase Agonist Design
GY Huang, OO Gerlits, MP Blakeley, B Sankaran, AY Kovalevsky, C Kim
Biochemistry 2014
Rare diseases in clinical endocrinology: a taxonomic classification system
G Marcucci, L Cianferotti, P Beck-Peccoz, M Capezzone, F Cetani, A Colao, MV Davì, E Uberti, SD Prato, R Elisei, A Faggiano, D Ferone, C Foresta, L Fugazzola, E Ghigo, G Giacchetti, F Giorgino, A Lenzi, P Malandrino, M Mannelli, C Marcocci, L Masi, F Pacini, G Opocher, A Radicioni, M Tonacchera, R Vigneri, MC Zatelli, ML Brandi
Journal of Endocrinological Investigation 2014
Mutation Analysis of Inhibitory Guanine Nucleotide Binding Protein Alpha (GNAI) Loci in Young and Familial Pituitary Adenomas
H Demir, I Donner, L Kivipelto, O Kuismin, C Schalin-Jäntti, ED Menis, A Karhu, PA Randazzo
PloS one 2014
The role of genetic and epigenetic changes in pituitary tumorigenesis.
Fukuoka H, Takahashi Y
Neurologia medico-chirurgica 2014
An N-ethyl-N-nitrosourea induced Corticotropin releasing hormone promoter mutation provides a mouse model for endogenous glucocorticoid excess
L Bentley, CT Esapa, MA Nesbit, RA Head, H Evans, D Lath, CL Scudamore, TA Hough, C Podrini, FM Hannan, WD Fraser, PI Croucher, MA Brown, SD Brown, RD Cox, RV Thakker
Endocrinology 2013
Carney Complex and McCune Albright Syndrome: An overview of clinical manifestations and human molecular genetics
P Salpea, CA Stratakis
Molecular and Cellular Endocrinology 2013
Inactivation of the Carney complex gene 1 (PRKAR1A) alters spatiotemporal regulation of cAMP and cAMP-dependent protein kinase: a study using genetically encoded FRET-based reporters
L Cazabat, B Ragazzon, A Varin, M Potier-Cartereau, C Vandier, D Vezzosi, M Risk-Rabin, A Guellich, J Schittl, P Lechene, W Richter, VO Nikolaev, J Zhang, J Bertherat, G Vandecasteele
Human Molecular Genetics 2013
The transcriptome that mediates increased cyclic adenosine monophosphate signaling in PRKAR1A defects and other settings
MF Azevedo, CA Stratakis
Endocrine Practice 2011
Cell-type specific expression of a dominant negative PKA mutation in mice
BS Willis, CM Niswender, T Su, PS Amieux, GS McKnight
PloS one 2011
The differential diagnosis of familial lentiginosis syndromes
MB Lodish, CA Stratakis
Familial Cancer 2011
Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes
FJ Rodriguez, CA Stratakis, DG Evans
Acta Neuropathologica 2011
Pancreatic ductal and acinar cell neoplasms in Carney complex: a possible new association
S Gaujoux, F Tissier, B Ragazzon, V Rebours, E Saloustros, K Perlemoine, C Vincent-Dejean, G Meurette, E Cassagnau, B Dousset, X Bertagna, A Horvath, B Terris, JA Carney, CA Stratakis, J Bertherat
The Journal of clinical endocrinology and metabolism 2011
Cushing's syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice
I Sahut-Barnola, C Joussineau, P Val, S Lambert-Langlais, C Damon, AM Lefrançois-Martinez, JC Pointud, G Marceau, V Sapin, F Tissier, B Ragazzon, J Bertherat, LS Kirschner, CA Stratakis, A Martinez
PLoS genetics 2010
Thyroid cancer: current molecular perspectives
F Giusti, A Falchetti, F Franceschelli, F Marini, A Tanini, ML Brandi
Journal of Oncology 2010
Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update
A Horvath, J Bertherat, L Groussin, M Guillaud-Bataille, K Tsang, L Cazabat, R Libé, E Remmers, F René-Corail, FR Faucz, E Clauser, A Calender, X Bertagna, JA Carney, CA Stratakis
Human Mutation 2010
Structure of D-AKAP2:PKA RI complex: insights into AKAP specificity and selectivity
GN Sarma, FS Kinderman, C Kim, S Daake, L Chen, BC Wang, SS Taylor
Structure (London, England : 1993) 2010
Interaction of the regulatory subunit of the cAMP-dependent protein kinase with PATZ1 (ZNF278)
WL Yang, R Ravatn, K Kudoh, L Alabanza, KV Chin
Biochemical and Biophysical Research Communications 2010
Familial Micronodular Adrenocortical Disease, Cushing Syndrome, and Mutations of the Gene Encoding Phosphodiesterase 11A4 (PDE11A)
JA Carney, RC Gaillard, J Bertherat, CA Stratakis
The American Journal of Surgical Pathology 2010
Carney complex and other conditions associated with micronodular adrenal hyperplasias
MQ Almeida, CA Stratakis
Best practice & research. Clinical endocrinology & metabolism 2010
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009
Mouse model for bilateral adrenal hyperplasia
I Sahut-Barnola, CD Joussineau, P Val, S Lambert-Langlais, AM Lefrançois-Martinez, JC Pointud, G Marceau, V Sapin, B Ragazzon, J Bertherat, LS Kirschner, CA Stratakis, A Martinez
Annales d'Endocrinologie 2009
Novel Isoform-specific Interfaces Revealed by PKA RIIβ Holoenzyme Structures
SH Brown, J Wu, C Kim, K Alberto, SS Taylor
Journal of Molecular Biology 2009
Analysis of GNAS1 and PRKAR1A gene mutations in human cardiac myxomas not associated with multiple endocrine disorders
G Mantovani, S Bondioni, S Corbetta, L Menicanti, B Rubino, E Peverelli, P Labarile, C DallAsta, B Ambrosi, P Beck-Peccoz, AG Lania, A Spada
Journal of Endocrinological Investigation 2009
Targeted deletion of Prkar1a reveals a role for protein kinase A in mesenchymal-to-epithelial transition
KS Nadella, GN Jones, A Trimboli, CA Stratakis, G Leone, LS Kirschner
Cancer research 2008
Unraveling the molecular basis of micronodular adrenal hyperplasia
A Horvath, CA Stratakis
Current opinion in endocrinology, diabetes, and obesity 2008
A novel PRKAR1A mutation associated with hepatocellular carcinoma in a young patient and a variable Carney complex phenotype in affected subjects in older generations
M Gennari, CA Stratakis, A Hovarth, P Pirazzoli, A Cicognani
Clinical Endocrinology 2008
Mutation of Prkar1a Causes Osteoblast Neoplasia Driven by Dysregulation of Protein Kinase A
E Pavel, K Nadella, WH Towns, LS S.
Molecular Endocrinology 2008
Regulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) and BIG2 activity via PKA and protein phosphatase 1gamma
F Kuroda, J Moss, M Vaughan
Proceedings of the National Academy of Sciences 2007
The Variations in the Immunologic Features and Interleukin-6 Levels for the Surgical Treatment of Cardiac Myxomas
H Yokomuro, K Yoshihara, Y Watanabe, N Shiono, N Koyama, Y Takanashi
Surgery Today 2007
Multiple cerebral cavernous malformations associated with extracranial mesenchymal anomalies
A Ardeshiri, A Ardeshiri, A Beiras-Fernandez, OK Steinlein, PA Winkler
Neurosurgical Review 2007
Familial pituitary adenomas with a heterogeneous functional pattern: Clinical and genetic features
G Raverot, W Arnous, A Calender, J Trouillas, G Sassolas, C Bournaud, M Pugeat, F Borson-Chazot
Journal of Endocrinological Investigation 2007
Carney complex (CNC)
J Bertherat
Orphanet Journal of Rare Diseases 2006
PRKAR1A mutations in primary pigmented nodular adrenocortical disease
L Cazabat, B Ragazzon, L Groussin, J Bertherat
Pituitary 2006
Haploinsufficiency at the Protein Kinase A RIα Gene Locus Leads to Fertility Defects in Male Mice and Men
KA Burton, DA McDermott, D Wilkes, MN Poulsen, MA Nolan, M Goldstein, CT Basson, GS McKnight
Molecular Endocrinology 2006
Assay Principle for Modulators of Protein−Protein Interactions and Its Application to Non-ATP-Competitive Ligands Targeting Protein Kinase A
SA Saldanha, G Kaler, HB Cottam, R Abagyan, SS Taylor
Analytical Chemistry 2006
Primary pigmented nodular adrenocortical disease associated with Carney complex: case report and literature review
FT Gonçalves, TC Feibelmann, CM Mendes, ML Fernandes, GH de Miranda, AP Gouvêa, PT Jorge
Sao Paulo Medical Journal 2006
A six month mitotane course induced sustained correction of hypercortisolism in a young woman with PPNAD and Carney complex
M Cignarelli, G Picca, M Campo, M Margaglione, A Marino, F Logoluso, F Giorgino
Journal of Endocrinological Investigation 2005
Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice
M Veugelers, D Wilkes, K Burton, DA McDermott, Y Song, MM Goldstein, KL Perle, CJ Vaughan, A O'Hagan, KR Bennett, BJ Meyer, E Legius, M Karttunen, R Norio, H Kaariainen, M Lavyne, JP Neau, G Richter, K Kirali, A Farnsworth, K Stapleton, P Morelli, Y Takanashi, JS Bamforth, F Eitelberger, I Noszian, W Manfroi, J Powers, Y Mochizuki, T Imai, GT Ko, DA Driscoll, E Goldmuntz, JM Edelberg, A Collins, D Eccles, AD Irvine, GS McKnight, CT Basson
Proceedings of the National Academy of Sciences 2004
Mechanisms for pituitary tumorigenesis: the plastic pituitary
S Melmed
Journal of Clinical Investigation 2003
Amino acid variant in the kinase binding domain of dual-specific A kinase-anchoring protein 2: a disease susceptibility polymorphism
S Kammerer, LL Burns-Hamuro, Y Ma, SC Hamon, JM Canaves, MM Shi, MR Nelson, CF Sing, CR Cantor, SS Taylor, A Braun
Proceedings of the National Academy of Sciences 2003
Designing isoform-specific peptide disruptors of protein kinase A localization
LL Burns-Hamuro, Y Ma, S Kammerer, U Reineke, C Self, C Cook, GL Olson, CR Cantor, A Braun, SS Taylor
Proceedings of the National Academy of Sciences 2003
Molecular Analysis of the Cyclic AMP-Dependent Protein Kinase A (PKA) Regulatory Subunit 1A (PRKAR1A) Gene in Patients with Carney Complex and Primary Pigmented Nodular Adrenocortical Disease (PPNAD) Reveals Novel Mutations and Clues For Pathophysiology: Augmented PKA Signaling is Associated with Adrenal Tumorigenesis in PPNAD
Groussin L, Kirschner LS, Vincent-Dejean C, Perlemoine K, Jullian E, Delemer B, Zacharieva S, Pignatelli D, Carney JA, Luton JP, Bertagna X, Stratakis CA, Bertherat J
The American Journal of Human Genetics 2002
Tumor Suppressor Loss in Pituitary Tumors
JM Alexander
Brain Pathology 2001
Genetics of the development and function of the adrenal cortex
K L Parker, B P Schimmer
Reviews in Endocrine and Metabolic Disorders 2001
Familial Nonmedullary Thyroid Neoplasia
HR Harach
Endocrine Pathology 2001

← Previous 1 2 3 Next →

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts