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

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 muta...

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Autores principales: Charnay, Théo, Mougel, Gregory, Amouroux, Cyril, Gueorguieva, Iva, Joubert, Florence, Pertuit, Morgane, Reynaud, Rachel, Barlier, Anne, Brue, Thierry, Saveanu, Alexandru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987334/
https://www.ncbi.nlm.nih.gov/pubmed/36890856
http://dx.doi.org/10.3389/fendo.2022.1080649
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author Charnay, Théo
Mougel, Gregory
Amouroux, Cyril
Gueorguieva, Iva
Joubert, Florence
Pertuit, Morgane
Reynaud, Rachel
Barlier, Anne
Brue, Thierry
Saveanu, Alexandru
author_facet Charnay, Théo
Mougel, Gregory
Amouroux, Cyril
Gueorguieva, Iva
Joubert, Florence
Pertuit, Morgane
Reynaud, Rachel
Barlier, Anne
Brue, Thierry
Saveanu, Alexandru
author_sort Charnay, Théo
collection PubMed
description 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.
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spelling pubmed-99873342023-03-07 A novel TBX19 gene mutation in patients with isolated ACTH deficiency from distinct families with a common geographical origin Charnay, Théo Mougel, Gregory Amouroux, Cyril Gueorguieva, Iva Joubert, Florence Pertuit, Morgane Reynaud, Rachel Barlier, Anne Brue, Thierry Saveanu, Alexandru Front Endocrinol (Lausanne) Endocrinology 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. Frontiers Media S.A. 2023-02-15 /pmc/articles/PMC9987334/ /pubmed/36890856 http://dx.doi.org/10.3389/fendo.2022.1080649 Text en Copyright © 2023 Charnay, Mougel, Amouroux, Gueorguieva, Joubert, Pertuit, Reynaud, Barlier, Brue and Saveanu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Charnay, Théo
Mougel, Gregory
Amouroux, Cyril
Gueorguieva, Iva
Joubert, Florence
Pertuit, Morgane
Reynaud, Rachel
Barlier, Anne
Brue, Thierry
Saveanu, Alexandru
A novel TBX19 gene mutation in patients with isolated ACTH deficiency from distinct families with a common geographical origin
title A novel TBX19 gene mutation in patients with isolated ACTH deficiency from distinct families with a common geographical origin
title_full A novel TBX19 gene mutation in patients with isolated ACTH deficiency from distinct families with a common geographical origin
title_fullStr A novel TBX19 gene mutation in patients with isolated ACTH deficiency from distinct families with a common geographical origin
title_full_unstemmed A novel TBX19 gene mutation in patients with isolated ACTH deficiency from distinct families with a common geographical origin
title_short A novel TBX19 gene mutation in patients with isolated ACTH deficiency from distinct families with a common geographical origin
title_sort novel tbx19 gene mutation in patients with isolated acth deficiency from distinct families with a common geographical origin
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9987334/
https://www.ncbi.nlm.nih.gov/pubmed/36890856
http://dx.doi.org/10.3389/fendo.2022.1080649
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