The final, formatted version of the article will be published soon.
CASE REPORT article
Front. Neurol.
Sec. Neurogenetics
Volume 15 - 2024 |
doi: 10.3389/fneur.2024.1344018
This article is part of the Research Topic Case Reports in Neurogenetics, volume III - 2023 View all 20 articles
Compound heterozygous variants detected by Next Generation Sequencing in a Tunisian child with Ataxia-Telangiectasia
Provisionally accepted- 1 Centre of Biotechnology of Sfax, Sfax, Tunisia
- 2 Hedi Chaker Hospital, Sfax, Tunisia
Ataxia-Telangiectasia (A-T) is an autosomal recessive primary immunodeficiency disorder (PID) caused by biallelic mutations occurring in the serine/threonine protein kinase (ATM) gene. The major role of nuclear ATM is the coordination of cell signaling pathways in response to DNA double-strand breaks, oxidative stress, and cell cycle checkpoints. Defect in ATM functions leads to A-T syndrome with phenotypic heterogeneity. Our study reports a case of a Tunisian girl with A-T carrying a compound heterozygous mutation c.[3894dupT];p.(Ala1299Cysfs3;rs587781823), with a splice acceptor variant: c.[5763-2A>C;rs876659489] in ATM gene that were identified by NGS. Further genetic analysis of the family, showed that the mother carried the c.[5763-2A>C] splice acceptor variant while the father harbored the c.[3894dupT] variant, at the heterozygous state.Molecular analysis provides the opportunity for accurate diagnosis and timely management in A-T patients with chronic progressive disease, especially infections and the risk of malignancies. This study characterizes for the first time the identification by NGS of compound heterozygous ATM pathogenic variants in a Tunisian A-T patient. Our study outlines the importance of molecular genetic testing for A-T patients which is required for earlier detection and reducing the burden of disease in the future using the patients' families.
Keywords: ataxia-telangiectasia, ATM, mutations, next generation sequencing, targeted sequencing
Received: 24 Nov 2023; Accepted: 08 May 2024.
Copyright: © 2024 Ammous-Boukhris, Abdelmaksoud-Dammak, Ben Ayed, Souhir, Olfa, Kamoun, Charfi Triki and Mokdad-Gargouri. 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) or licensor 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.
* Correspondence:
Raja Mokdad-Gargouri, Centre of Biotechnology of Sfax, Sfax, Tunisia
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.