A novel TBX19 gene mutation in patients with isolated ACTH deficiency from distinct families with a common geographical origin.

Autor:	Charnay T; Institut National de la Santé et de la Recherche Médicale (INSERM) U1251, Marseille Medical Genetics (MMG), Institut Marseille Maladies Rares (MarMaRa), Aix-Marseille Université, Marseille, France.; Laboratory of Molecular Biology, Centre Hospitalier Universitaire Conception, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France., Mougel G; Institut National de la Santé et de la Recherche Médicale (INSERM) U1251, Marseille Medical Genetics (MMG), Institut Marseille Maladies Rares (MarMaRa), Aix-Marseille Université, Marseille, France.; Laboratory of Molecular Biology, Centre Hospitalier Universitaire Conception, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France., Amouroux C; Paediatric Department, Endocrinology Unit, Arnaud de Villeneuve Hospital, Montpellier University Hospital, Montpellier, France., Gueorguieva I; Paediatric Department, Endocrinology Unit, Children's Center, Jeanne-de-Flandre Hospital, Lille University Hospital, Lille, France., Joubert F; Department of Pediatrics, Centre Hospitalier d'Avignon, Avignon, France., Pertuit M; Laboratory of Molecular Biology, Centre Hospitalier Universitaire Conception, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France., Reynaud R; Institut National de la Santé et de la Recherche Médicale (INSERM) U1251, Marseille Medical Genetics (MMG), Institut Marseille Maladies Rares (MarMaRa), Aix-Marseille Université, Marseille, France.; Department of Multidisciplinary Peadiatrics, Centre de Référence des Maladies Rares d'origine hypophysaire HYPO, Hôpital Timone-Enfants, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France., Barlier A; Institut National de la Santé et de la Recherche Médicale (INSERM) U1251, Marseille Medical Genetics (MMG), Institut Marseille Maladies Rares (MarMaRa), Aix-Marseille Université, Marseille, France.; Laboratory of Molecular Biology, Centre Hospitalier Universitaire Conception, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France., Brue T; Institut National de la Santé et de la Recherche Médicale (INSERM) U1251, Marseille Medical Genetics (MMG), Institut Marseille Maladies Rares (MarMaRa), Aix-Marseille Université, Marseille, France.; Department of Endocrinology, Centre de Référence des Maladies Rares de l'hypophyse HYPO, Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France., Saveanu A; Institut National de la Santé et de la Recherche Médicale (INSERM) U1251, Marseille Medical Genetics (MMG), Institut Marseille Maladies Rares (MarMaRa), Aix-Marseille Université, Marseille, France.; Laboratory of Molecular Biology, Centre Hospitalier Universitaire Conception, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2023 Feb 15; Vol. 13, pp. 1080649. Date of Electronic Publication: 2023 Feb 15 (Print Publication: 2022).
DOI:	10.3389/fendo.2022.1080649
Abstrakt:	Isolated ACTH deficiency (IAD) is a life-threatening condition, particularly in the neonatal period, while a main consequence of undiagnosed isolated ACTH deficiency in survivors is cognitive impairment. TBX19 is involved in the differentiation and proliferation of corticotropic cells and TBX19 mutations are responsible for more than 60% of neonatal cases of IAD. We describe a new variant of the main TBX19 transcript (NM 005149.3, c.840del (p.(Glu280Asp fs*27)), classified as pathogenic, whose pathogenicity is assumed to be due to nonsense mediated decay leading to non-expression of T-box transcription factor TBX19. Moreover we summarize the TBX19 mutations published as individual cases since our last large cohort. Interestingly, this pathogenic variant was identified in four patients from three apparently unrelated families. Two of these families were consanguineous, and after investigations all of three were discovered to have roots in the same mountainous region of northern Morocco, suggesting a founder effect. Early diagnosis, timely treatment (hydrocortisone therapy) and preventive education allowed normal development, growth and quality of life in all patients. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Charnay, Mougel, Amouroux, Gueorguieva, Joubert, Pertuit, Reynaud, Barlier, Brue and Saveanu.)
Databáze:	MEDLINE
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