Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/388
Title: A PRKAR1A Mutation Associated with Primary Pigmented Nodular Adrenocortical Disease in 12 Kindreds
Authors: Groussin, Lionel
Horvath, Anelia
Jullian, Eric
Boikos, Sosipatros
Rene-Corail, Fernande
Lefebvre, Herve
Cephise-Velayoudom, Fritz-Line
Vantyghem, Marie-Cristine
Chanson, Philippe
Conte-Devolx, Bernard
Lucas, Miguel
Gentil, Alfonso
Malchoff, Carl D
Tissier, Frédérique
Carney, J Aidan
Bertagna, Xavier
Stratakis, Constantine A
Bertherat, Jérôme
metadata.dc.contributor.authoraffiliation: [Groussin,L; Jullian,E; Rene-Corail,F; Tissier,F; Bertagna,X; Bertherat,J] Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique Unité Mixte de Recherche. Institut Cochin, Université René-Descartes, Paris, France. [Groussin,L; Bertagna,X; Bertherat,J] Department of Endocrinology, Centre de Référence Maladies Rares de la Surrénale, Hôpital Cochin, Paris, France. [Horvath,A; Boikos,S; Stratakis,CA] Section on Endocrinology and Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. [Lefebvre,H] Department of Endocrinology, Centre Hospitalier Universitaire de Rouen, France.[Cephise-Velayoudom,FL; Vantyghem,MC] Department of Endocrinology, Clinique Marc Linquette-Centre Hospitalier Universitaire, Lille, France. [Chanson,P] Department of Endocrinology, Kremlin Bicetre, France. [Conte-Devolx,B] Department of Endocrinology, Hôpital de la Timone Marseille, France. [Lucas,M] Department of Molecular Biology Hospital Universitario Virgen Macarena, Seville, Spain. [Gentil,A] Department of Endocrinology, Hospital Universitario Virgen Macarena, Seville, Spain.[Malchoff,CD] Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut. [Tissier,F] Department of Pathology , Hôpital Cochin, Paris, France. [Carney,JA] Emeritus Staff, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Keywords: mutation;disease;primary pigmented nodular adrenocortical
metadata.dc.subject.mesh: Medical Subject Headings::Diseases::Endocrine System Diseases::Adrenal Gland Diseases::Adrenal Cortex Diseases
Medical Subject Headings::Anatomy::Cells::Cells, Cultured
Medical Subject Headings::Diseases::Endocrine System Diseases::Adrenal Gland Diseases::Adrenocortical Hyperfunction::Cushing Syndrome
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Cyclic Nucleotide-Regulated Protein Kinases::Cyclic AMP-Dependent Protein Kinases::Cyclic AMP-Dependent Protein Kinase Type I::Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Cyclic Nucleotide-Regulated Protein Kinases::Cyclic AMP-Dependent Protein Kinases
Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Piperidines::Piperidones::Cycloheximide
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Founder Effect
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger
Issue Date: May-2006
Publisher: Endocrine Society
Citation: Groussin L, Horvath A, Jullian E, Boikos S, Rene-Corail F, Lefebvre H, et al. A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds. J Clin Endocrinol Metab. 2006 May;91(5):1943-9.
Abstract: CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD), a rare cause of corticotropin-independent Cushing syndrome, can be part of Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac myxomas, and endocrine tumors or be isolated (i). Germline PRKAR1A-inactivating mutations have been observed in both CNC and iPPNAD, but with no apparent genotype-phenotype correlation. OBJECTIVE:The objectives of the study were a detailed phenotyping for CNC manifestations in 12 kindreds bearing the same PRKAR1A mutation and a study of the consequences of the mutation and a potential founder effect. DESIGN: The study consisted of descriptive case reports. SETTING: The study was conducted at two referral centers. PATIENTS: The patients described in this study were referred for PRKAR1A gene mutation analysis because of a diagnosis of apparently iPPNAD. RESULTS: We describe a 6-bp polypyrimidine tract deletion [exon 7 IVS del (-7-->-2)] in 12 unrelated kindreds that were referred for Cushing syndrome due to PPNAD. Nine of the patients had no family history; in two, there was a family history of iPPNAD. Only one patient met the criteria for CNC. Relatives carrying the same mutation had no manifestations of CNC or PPNAD, suggesting a low penetrance of this PRKAR1A defect. A founder effect was excluded by extensive genotyping of chromosome 17 markers. CONCLUSIONS: In conclusion, a small intronic deletion of the PRKAR1A gene is a low-penetrance cause of mainly iPPNAD; it is the first PRKAR1A genetic defect to have an association with a specific phenotype.
URI: http://hdl.handle.net/10668/388
metadata.dc.relation.publisherversion: http://jcem.endojournals.org/content/91/5/1943
metadata.dc.identifier.doi: 10.1210/jc.2005-2708
ISSN: 0021-972X
Appears in Collections:01- Artículos - Hospital Virgen Macarena

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