Heidari Masoud, Soleyman-Nejad Morteza, Taskhiri Mohammad H, Shahpouri Javad, Isazadeh Alireza, Ahangari Roghayyeh, Mohamadi Ali R, Ebrahimi Masoumeh, Karimi Hadi, Bolhassani Manzar, Karimi Zahra, Heidari Mansour
1Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran; 2Ariagene Medical Genetics Laboratory, Qom, Iran; 3Pediatric Clinical Research of Development Center, Qom University of Medical Sciences, Qom, Iran; 4Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 5Nekouei-Hedayati-Forghani Hospital, Department of Obstetrics and Gynecology, Qom University of Medical Sciences, Qom, Iran; 6Qom Social Welfare and Rehabilitation Center, Qom, Iran; 7Department of Medical Genetics, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Curr Genomics. 2019 Nov;20(7):531-534. doi: 10.2174/1389202920666191107153734.
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 Ataxia-telangiectasia.
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.
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.
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.
共济失调毛细血管扩张症（AT）是儿童期最常见的常染色体隐性遗传性共济失调之一。AT的致病基因ATM（AT，突变型）编码一种参与细胞周期检查点及其他对基因毒性反应的蛋白质。我们在两个不相关的患有共济失调毛细血管扩张症的伊朗家庭中描述了两个新的致病突变。
先证者包括一名6岁女性和一名18岁男性，分别来自两个不同的伊朗家庭，均被诊断为共济失调毛细血管扩张症。在本研究中，采用全外显子组测序（WES）检测先证者的基因变化。通过PCR直接测序对家庭中变异与疾病的共分离情况进行分析。
利用全外显子组测序（WES）在先证者中检测到共济失调毛细血管扩张症突变型ATM基因的两个新的移码突变，即（c.4236_4236del p.Pro1412fs）和（c.8907T>G p.Tyr2969Ter）。这些突变在两个独立的A-T家庭中被观察到。
下一代测序成功鉴定出共济失调毛细血管扩张症家庭中的致病突变。本研究报道的ATM基因中的这些新突变可为AT的遗传咨询、植入前基因诊断（PGD）和产前诊断（PND）提供帮助。
