A Novel ATM Gene Variant (c.4940T>G; p.Leu1647Arg) in a Child with Ataxia–Telangiectasia: Clinical, Radiologic, and Genetic Correlation

Ataxia–telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ATM gene, characterized by progressive cerebellar ataxia, telangiectasias, immunodeficiency, and increased cancer risk. Reporting novel ATM variants is essential to refine genotype–phenotype correlations. We report a 6-year-old boy presenting with progressive gait ataxia, recurrent respiratory infections, chronic otorrhea, and conjunctival telangiectasias. Laboratory studies revealed immunodeficiency with reduced IgG and IgA, and elevated IgM. Brain MRI showed mild cerebellar atrophy, while chest X-ray revealed bilateral interstitial infiltrates. Whole-exome sequencing identified a novel homozygous missense variant in ATM (c.4940T>G; p.Leu1647Arg), classified as a variant of uncertain significance but predicted deleterious by in silico tools. The patient improved with intravenous antibiotics and IVIG. Family genetic testing was recommended given parental consanguinity and an affected sibling. This case illustrates the classical phenotype of A-T with immunodeficiency and neurological dysfunction, combined with a novel ATM variant not previously reported in population databases. Such cases expand the known mutational spectrum and may guide diagnosis and counseling. Although the variant’s pathogenicity remains to be functionally validated, its clinical correlation supports disease relevance. Identification of novel ATM variants is crucial for advancing diagnostic precision, genetic counseling, and future therapeutic strategies in A-T.