A novel splice site mutation of the ATM gene associated with ataxia telangiectasia

Kolsoum Saeidi, Nasrollah Saleh-gohari, Seyed Ebrahim Mansouri Nejad




Objective: Ataxia telangiectasia (AT) is a rare autosomal recessive disorder caused by mutation in the Ataxia telangiectasia mutated (ATM) gene. This disorder is characterized by progressive cerebellar ataxia, telangiectasia, immunodeficiency and a predisposition to leukemia/lymphoma.

Methods: In this study, four members of a family including a symptomatic AT patient, his parents and sibling were examined for ATM gene defects. DNA was extracted from peripheral leukocytes and the coding regions and exon-intron boundaries of ATM gene were amplified by next generation sequencing technique. The identified mutation was tested in all members of the family.  

Results: Molecular analyses identified a homozygous T to G substitution in c.7308-6 position resulting in a novel acceptor splice site in intron 49 of the ATM gene in the index patient. Parents and sibling of the proband were heterozygous for the same mutation.

Conclusions: The variant c.7308-6T>G is predicted to be pathogenic due to impaired splice site causing exon skipping. This newly found frameshift mutation cosegregated as an autosomal recessive trait as expected for Ataxia telangiectasia syndrome.




Ataxia telangiectasia, cerebellar ataxia, splicing, mutation, gene, chromosome, autosomal recessive

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DOI: https://doi.org/10.22037/ijcn.v12i4.15397


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