A novel splice site mutation of the ATM gene associated with ataxia telangiectasia
Iranian Journal of Child Neurology,
Vol. 12 No. 4 (2018),
1 October 2018
,
Page 111-119
https://doi.org/10.22037/ijcn.v12i4.15397
Abstract
Abstract
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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