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

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.