Masoud Heidari, Morteza Soleyman-Nejad, Mohammad H. Taskhiri, Javad Shahpouri, Alireza Isazadeh, Roghayyeh Ahangari, Ali R. Mohamadi, Masoumeh Ebrahimi , Hadi Karimi , Manzar Bolhassani, Zahra Karimi and Mansour Heidari * Pages 531 - 534 ( 4 )
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.
Ataxia-telangiectasia, mutation detection, whole exome sequencing, protein, probands, frameshift mutations.
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Ariagene Medical Genetics Laboratory, Qom, Ariagene Medical Genetics Laboratory, Qom, Pediatric Clinical Research of Development Center, Qom University of Medical Sciences, Qom, Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Nekouei- Hedayati-Forghani Hospital, Department of Obstetrics and Gynecology, Qom University of Medical Sciences, Qom, Qom Social Welfare and Rehabilitation Center, Qom, Qom Social Welfare and Rehabilitation Center, Qom, Qom Social Welfare and Rehabilitation Center, Qom, Ariagene Medical Genetics Laboratory, Qom, Ariagene Medical Genetics Laboratory, Qom, Ariagene Medical Genetics Laboratory, Qom