Identification of novel genetic variants in phosphodiesterase 8B (PDE8B), a cAMP-specific phosphodiesterase highly expressed in the adrenal cortex, in a cohort of patients with adrenal tumours
| Autor: | Maya Lodish, Maria Nesterova, Amato Fratticci, Isaak Levy, Anelia Horvath, Delphine Vezzosi, Fabio R. Faucz, Monalisa F. Azevedo, Constantine A. Stratakis, Rossella Libé, Anya Rothenbuhler, Marie Sanson, Jérôme Bertherat, Madson Q. Almeida |
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| Rok vydání: | 2012 |
| Předmět: |
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medicine.medical_specialty Endocrinology Diabetes and Metabolism In silico Adrenal Gland Neoplasms Biology Article symbols.namesake Endocrinology Internal medicine Genetic variation medicine Humans Genetic Predisposition to Disease Gene Sanger sequencing Adrenal cortex Reverse Transcriptase Polymerase Chain Reaction Case-control study Phosphodiesterase Genetic Variation Transfection medicine.anatomical_structure 3' 5'-Cyclic-AMP Phosphodiesterases Case-Control Studies symbols Adrenal Cortex Female |
| Zdroj: | Clinical endocrinology. 77(2) |
| ISSN: | 1365-2265 |
| Popis: | SummaryBackground Genetic aberrations in various components of cAMP signalling pathway predispose to endocrine tumours. Mutations in the phosphodiesterases (PDEs) are involved in the predisposition to adrenocortical neoplastic conditions. Objective To screen for genetic variations in PDE8B among patients with different types of adrenocortical tumours. Design and subjects This is a case–control study followed by functional analyses. Two hundred and sixteen unrelated patients with different types of adrenocortical tumours and 192 healthy control individuals participated in the study. Methods Bidirectional Sanger sequencing, in vitro cell line transfection and in silico modelling are used in this study. Results Nine different PDE8B sequence changes, six novel and three previously reported, were identified in our patients and controls. Two of the variations, seen only in the patient group, showed significant potential to impair protein function, both in vitro and in silico. Conclusion PDE8B is another PDE gene in which variations may contribute to predisposition of adrenocortical tumours. |
| Databáze: | OpenAIRE |
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