AUTHOR=Ammous-Boukhris Nihel , Abdelmaksoud-Dammak Rania , Ben Ayed-Guerfali Dorra , Guidara Souhir , Jallouli Olfa , Kamoun Hassen , Charfi Triki Chahnez , Mokdad-Gargouri Raja 

TITLE=Case report: Compound heterozygous variants detected by next-generation sequencing in a Tunisian child with ataxia-telangiectasia

JOURNAL=Frontiers in Neurology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1344018

DOI=10.3389/fneur.2024.1344018

ISSN=1664-2295

ABSTRACT=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.