Ataxia-Telangiectasia with novel splice site mutation in the ATM gene

Introduction: Ataxia telangiectasia (AT) is a rare autosomal recessive disorder caused by mutation in the Ataxiatelangiectasia 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 siblingwere examined for ATM gene defects. DNA was extracted from peripheral leukocytes and the coding regionsand exon-intron boundaries of ATM gene were amplified by next generation sequencing technique. Theidentified 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 anovel acceptor splice site in intron 49 of the ATM gene in the index patient. Parents and sibling of the probandwere heterozygous for the same mutation.Conclusions: The variant c.7308-6T> G is predicted to be pathogenic due to impaired splice site causing exonskipping. This newly found splicing mutation cosegregated as an autosomal recessive trait as expected for Ataxiatelangiectasia syndrome.

Keywords:

Ataxia telangiectasia , Cerebellar ataxia , Splice site , New mutation , Autosomal recessive