Germline mutations in the thyrotropin receptor gene cause non–autoimmune autosomal dominant hyperthyroidism
| Autor: | Jasmine Parma, J Leclère, Jacques Emile Dumont, J. Orgiazzi, Claire Schvartz, Marc Decoulx, Jacqueline Van Sande, A Allgeier, Marie-Joëlle Delisle, Laurence Duprez, Gilbert Vassart |
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| Rok vydání: | 1994 |
| Předmět: |
Adenoma
Male Models Molecular endocrine system medicine.medical_specialty endocrine system diseases Protein Conformation DNA Mutational Analysis Molecular Sequence Data Biology Transfection medicine.disease_cause Hyperthyroidism Second Messenger Systems Germline Cell Line Thyrotropin receptor Adenylyl cyclase chemistry.chemical_compound Germline mutation Internal medicine Chlorocebus aethiops Cyclic AMP Genetics medicine Animals Humans Point Mutation Amino Acid Sequence Thyroid Neoplasms Receptor Genes Dominant Mutation Base Sequence Thyroid Wild type Receptors Thyrotropin Pedigree Enzyme Activation medicine.anatomical_structure Endocrinology chemistry Female France Adenylyl Cyclases |
| Zdroj: | Nature Genetics. 7:396-401 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng0794-396 |
| Popis: | The thyrotropin receptor (TSHR), a member of the large family of G protein-coupled receptors, controls both the function and growth of thyroid cells via stimulation of adenylyl cyclase. We report two different mutations in the TSHR gene of affected members of two large pedigrees with non-autoimmune autosomal dominant hyperthyroidism (toxic thyroid hyperplasia), that involve residues in the third (Val509Ala) and seventh (Cys672Tyr) transmembrane segments. When expressed by transfection in COS-7 cells, the mutated receptors display a higher constitutive activation of adenylyl cyclase than wild type. This new disease entity is the germline counterpart of hyperfunctioning thyroid adenomas, in which different somatic mutations with similar functional characteristics have been demonstrated. |
| Databáze: | OpenAIRE |
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