Clinically Symptomatic Resistance to Thyroid Hormone β Syndrome Because of THRB Gene Mosaicism.

Autor:	Donnars A; Department of Biochemistry and Molecular Biology, University Hospital Angers, Angers, France., Leplat A; Department of Biochemistry and Molecular Biology, University Hospital Angers, Angers, France., Grosheny C; Groupe Hospitalier Bretagne Sud, Lorient, France., Briet C; Department of Endocrinology, Diabetology and Nutrition, University Hospital Angers, Angers, France.; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France., Illouz F; Department of Endocrinology, Diabetology and Nutrition, University Hospital Angers, Angers, France.; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France., Bouzamondo N; Department of Biochemistry and Molecular Biology, University Hospital Angers, Angers, France.; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France., Moal V; Department of Biochemistry and Molecular Biology, University Hospital Angers, Angers, France.; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France., De Casson FB; Department of Biochemistry and Molecular Biology, University Hospital Angers, Angers, France.; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France., Bouhours-Nouet N; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France.; Department of Paediatric Endocrinology and Diabetology, University Hospital Angers, Angers, France., Coutant R; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France.; Department of Paediatric Endocrinology and Diabetology, University Hospital Angers, Angers, France.; Angers University, MITOVASC, INSERM, CNRS, Angers, France., Rodien P; Department of Endocrinology, Diabetology and Nutrition, University Hospital Angers, Angers, France.; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France.; Angers University, MITOVASC, INSERM, CNRS, Angers, France., Mirebeau-Prunier D; Department of Biochemistry and Molecular Biology, University Hospital Angers, Angers, France.; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France.; Angers University, MITOVASC, INSERM, CNRS, Angers, France., Dieu X; Department of Biochemistry and Molecular Biology, University Hospital Angers, Angers, France.; Centre de Référence des Maladies Rares de la Thyroïde et des Récepteurs Hormonaux, University Hospital Angers, Angers, France.; Angers University, MITOVASC, INSERM, CNRS, Angers, France.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2022 Aug 18; Vol. 107 (9), pp. e3548-e3552.
DOI:	10.1210/clinem/dgac347
Abstrakt:	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. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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