Department of Medical Genetics, School of Medicine, Tehran University of medical sciences, Tehran, Iran.
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
Pediatr Allergy Immunol. 2021 Aug;32(6):1316-1326. doi: 10.1111/pai.13461. Epub 2021 Mar 2.
Ataxia-telangiectasia (A-T) is a rare genetic disorder characterized by a distinct range of clinical manifestations, including progressive ataxia, immunodeficiency, and radiosensitivity.
Clinical data, laboratory results, and genetic data were collected from forty-three A-T patients. Whole-exome sequencing and Sanger sequencing were done for the patients clinically diagnosed as suffering from A-T. Based on the phenotype severity of the disease, patients were divided into severe and mild subgroups.
The median (IQR) age of diagnosis in this cohort was 5 (3-7) years, and various types of clinical manifestations, including fever (P =.005), lower respiratory tract infection (P = .033), diarrhea (P = .014), and hepatosplenomegaly (P = .032), were significantly higher among patients diagnosed with the severe phenotype. Our results showed a correlation between phenotype severity and mutation type. The chance of having severe phenotype in patients who have severe mutations, including frameshift and nonsense, was 7.3 times higher than in patients who were categorized in the mild genotype group (odds ratio = 7.3, P = .006). Thirty-four types of mutations including 9 novel mutations were observed in our study.
Molecular analysis provides the opportunity for accurate diagnosis and timely management in A-T patients with chronic progressive disease, especially infections and the risk of malignancies. This study characterizes for the first time the broad spectrum of mutations and phenotypes in Iranian A-T patients, which is required for carrier detection and reducing the burden of disease in the future using the patients' families and for the public healthcare system.
共济失调毛细血管扩张症（A-T）是一种罕见的遗传疾病，其特征是具有广泛的临床表现，包括进行性共济失调、免疫缺陷和辐射敏感性。
从 43 名 A-T 患者中收集了临床数据、实验室结果和遗传数据。对临床诊断为 A-T 的患者进行了全外显子组测序和 Sanger 测序。根据疾病表型严重程度，将患者分为严重和轻度亚组。
该队列的中位（IQR）诊断年龄为 5（3-7）岁，各种临床表现，包括发热（P =.005）、下呼吸道感染（P =.033）、腹泻（P =.014）和肝脾肿大（P =.032），在诊断为严重表型的患者中明显更高。我们的结果显示表型严重程度与突变类型之间存在相关性。具有严重突变（包括移码和无义）的患者发生严重表型的几率是轻度基因型组患者的 7.3 倍（优势比=7.3，P=.006）。在我们的研究中观察到包括 9 种新突变在内的 34 种突变类型。
分子分析为患有慢性进行性疾病的 A-T 患者提供了准确诊断和及时管理的机会，特别是感染和恶性肿瘤的风险。本研究首次描述了伊朗 A-T 患者的广泛突变和表型谱，这对于利用患者家庭进行携带者检测和减轻未来疾病负担以及公共医疗保健系统是必要的。
