Background: Ataxia telangiectasia (AT) is one of the most common autosomal recessive
hereditary ataxia presenting in childhood. The responsible gene for AT designated ATM (AT, mutated)
encodes a protein which is involved in cell cycle checkpoints and other responses to genotoxicity.
We describe two novel disease-causing mutations in two unrelated Iranian families with Ataxiatelangiectasia.
Methods: The probands including a 6-year-old female and an 18-year-old boy were diagnosed with
Ataxia-telangiectasia among two different Iranian families. In this study, Whole-Exome Sequencing
(WES) was employed for the detection of genetic changes in probands. The analysis of the cosegregation
of the variants with the disease in families was conducted using PCR direct sequencing.
Results: Two novel frameshift mutations, (c.4236_4236del p. Pro1412fs) and (c.8907T>G p.
Tyr2969Ter) in the ataxia telangiectasia mutated ATM gene were detected using Whole-Exome Sequencing
(WES) in the probands. These mutations were observed in two separate A-T families.
Conclusion: Next-generation sequencing successfully identified the causative mutation in families with
ataxia-telangiectasia. These novel mutations in the ATM gene reported in the present study could assist
genetic counseling, Preimplantation Genetic Diagnosis (PGD) and prenatal diagnosis (PND) of AT.