Clinically Symptomatic Resistance to Thyroid Hormone β Syndrome Because of THRB Gene Mosaicism
| Autor: | Anne Donnars, Alice Leplat, Catherine Grosheny, Claire Briet, Frédéric Illouz, Nathalie Bouzamondo, Valérie Moal, Florence Boux De Casson, Natacha Bouhours-Nouet, Régis Coutant, Patrice Rodien, Delphine Mirebeau-Prunier, Xavier Dieu |
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| Přispěvatelé: | Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Clinical Endocrinology and Metabolism Journal of Clinical Endocrinology and Metabolism, 2022, 107 (9), pp.e3548-e3552. ⟨10.1210/clinem/dgac347⟩ |
| ISSN: | 0021-972X 1945-7197 |
| DOI: | 10.1210/clinem/dgac347⟩ |
| Popis: | Context Resistance to thyroid hormone β syndrome (RTHβ) is caused by pathogenic variants in the THRB gene, but such variants are found in only 85% of cases. We report the case of a patient with RTHβ phenotype but for whom we found a pathogenic variant of the THRB gene in a mosaic state. Case Description The patient is a 52-year-old woman with clinical and biological signs of RTHβ. Symptoms included asthenia, cardiac palpitations, and diarrhea. Repeated thyroid function tests showed an elevated serum TSH, elevated serum free T4, and variably normal or slightly elevated serum fT3. Pituitary magnetic resonance imaging was normal, and the thyrotropin-releasing hormone test result was compatible with the diagnosis of RTHβ syndrome. Initial Sanger sequencing on blood samples could not highlight the presence of a mosaic variant because of insufficient sensitivity. When next-generation sequencing became accessible, blood samples were retested and we found a known pathogenic variant: c.949G > A; p.(ala317Thr), with an allelic frequency of 12%. Other samples from tissues of different embryological origin were also tested and found an allelic frequency of 5.7%, 17.9%, 9.9%, 6.4%, and 0% on urine tests, oral swab, nasal mucosa swab, skin biopsy, and conjunctival swab, respectively. Cloning confirmed the allelic frequency observed. Conclusions We highlight that a pathogenic variant in a mosaic state in the THRB gene may be the cause of an authentic RTHβ syndrome. High-throughput sequencing of multiple tissues eases the detection of pathogenic variant in a mosaic state and allows the correct diagnosis of patients with true RTHβ, thus avoiding patient mismanagement. |
| Databáze: | OpenAIRE |
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