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 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.

中文翻译：

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通过全外显子组测序鉴定共济失调-毛细血管扩张症患者 ATM 基因中的两种新突变

背景 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 指定的 ATM（AT，突变）的负责基因编码一种蛋白质，该蛋白质参与细胞周期检查点和其他对基因毒性的反应。我们描述了两个患有共济失调毛细血管扩张症的不相关伊朗家庭中的两种新的致病突变。方法先证者包括一名 6 岁女性和一名 18 岁男孩，在两个不同的伊朗家庭中被诊断为共济失调-毛细血管扩张症。在这项研究中，全外显子组测序 (WES) 被用于检测先证者的遗传变化。使用 PCR 直接测序对变异与家族疾病的共分离进行分析。结果 两个新的移码突变，(c.4236_4236del p. Pro1412fs) 和 (c. 8907T>G 页。在先证者中使用全外显子组测序（WES）检测共济失调毛细血管扩张症突变的 ATM 基因中的 Tyr2969Ter）。在两个独立的 AT 家族中观察到这些突变。结论二代测序成功鉴定了共济失调-毛细血管扩张家族的致病突变。本研究中报道的 ATM 基因中的这些新突变有助于 AT 的遗传咨询、胚胎植入前遗传学诊断 (PGD) 和产前诊断 (PND)。