Work

Molecular Analysis through Whole Exome Sequencing in Ataxia Telangiectasia Patients: Beyond ATM

Year: 2025

Type: article

Abstract: BACKGROUND: Ataxia-telangiectasia (AT) is a rare neurodegenerative disorder caused by biallelic ATM gene mutations. While most patients exhibit classical features-progressive ataxia, oculocutaneous telangiectasia, and oculomotor apraxia-atypical presentations and overlapping phenotypes with AT-like disorders pose diagnostic challenges. OBJECTIVES: To describe clinical and genetic findings in patients with suspected AT and assess the diagnostic utility of whole-exome sequencing (WES). METHODS: We analyzed 20 patients with clinical features suggestive of AT who underwent genomic evaluation. RESULTS: Pathogenic or likely pathogenic ATM variants were found in 14 /19 patients with available data. Three had mutations in MRE11A or PCNA, consistent with ATLD1 and ATLD2, respectively. Two patients with classic phenotypes lacked conclusive genetic findings. CONCLUSIONS: Our findings highlight the phenotypic and genetic heterogeneity of AT and limitations of WES. We propose the integration of whole-genome sequencing (WGS) and RNA sequencing as complementary tools to improve diagnostic yield in AT and AT-like syndromes.

Source: Movement Disorders Clinical Practice

DOI: 10.1002/mdc3.70418