Abstract

Introduction

Ataxia telangiectasia (A-T) is a rare autosomal recessive, multisystemic disease. Patients with the A-T syndrome present a broad spectrum of disease phenotypes. The ATM (ataxia telangiectasia mutated) gene, the only causative gene for A-T.

Method

A patient of Persian origin presenting with typical A-T was referred to our genetics centre for specialized genetic counselling and testing. Targeted next-generation sequencing (NGS) was applied. Sanger sequencing was used to confirm the candidate variant. Modelling was performed using the SWISS-MODEL server.

Results

A homozygous stop-gain variant c.829G > T (p.E277*) was found in the ATM gene. This variant was confirmed by Sanger sequencing and modelling of native structure, and truncated structure was performed.

Conclusion

To date, very few pathogenic variants of the ATM gene have been reported from the Iranian population. The finding has implications in molecular diagnostic for A-T in Iran.

中文翻译：

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新一代测序揭示了 ATM 基因中的一种新的致病变异

摘要

介绍

共济失调毛细血管扩张症（AT）是一种罕见的常染色体隐性遗传多系统疾病。AT 综合征患者表现出广泛的疾病表型。ATM （共济失调毛细血管扩张症突变）基因，是 AT的唯一致病基因。

方法

一位患有典型 AT 的波斯裔患者被转介到我们的遗传学中心进行专门的遗传咨询和测试。应用了靶向二代测序（NGS）。Sanger测序用于确认候选变体。使用 SWISS-MODEL 服务器进行建模。

结果

在ATM基因中发现了纯合终止增益变体 c.829G > T (p.E277*)。该变体通过 Sanger 测序和天然结构建模得到证实，并进行了截断结构。

结论

迄今为止，伊朗人群中很少有ATM基因致病变异的报道。这一发现对伊朗 AT 的分子诊断具有重要意义。