Identification of Two Novel Mutations in the Atm Gene From Patients With Ataxia-Telangiectasia by Whole Exome Sequencing Publisher



Heidari M¹ ; Soleymannejad M² ; Taskhiri MH² ; Shahpouri J³ ; Isazadeh A⁴ ; Ahangari R⁵ ; Mohamadi AR⁶ ; Ebrahimi M⁶ ; Karimi H⁶ ; Bolhassani M² ; Karimi Z² ; Heidari M¹
Source: Current Genomics Published:2019

Abstract

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, mu-tated) encodes a protein which is involved in cell cycle checkpoints and other responses to genotoxic-ity. We describe two novel disease-causing mutations in two unrelated Iranian families with Ataxia-telangiectasia. 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 co-segregation 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. ©2019 Bentham Science Publishers.