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Updated: Jan 6, 2026
Author Spotlight: Deciphering the Role of ATM in Ataxia-Telangiectasia and the Associated Cerebellar Degeneration
Published on: December 27, 2024
Molecular Analysis through Whole Exome Sequencing in Ataxia Telangiectasia Patients: Beyond ATM
Luiz Eduardo Novis1, Luane Abdalla Gouvea1, Thiago Yoshinaga Tonholo Silva1
1Department of Neurology, Ataxia Unit, Universidade Federal de São Paulo, São Paulo, Brazil.
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.
