The spectrum of ATM gene mutations in Iranian patients with ataxia‐telangiectasia

• Published in: Pediatric allergy and immunology Vol. 32; no. 6; pp. 1316 - 1326
• Main Authors: Amirifar, Parisa, Ranjouri, Mohammad Reza, Pashangzadeh, Salar, Lavin, Martin, Yazdani, Reza, Moeini Shad, Tannaz, Mehrmohamadi, Mahya, Salami, Fereshte, Delavari, Samaneh, Moamer, Soraya, Aghamohammadi, Asghar, Akrami, Seyed Mohammad, Abolhassani, Hassan
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2021
• Subjects: Ataxia; Ataxia telangiectasia; Ataxia Telangiectasia - diagnosis; Ataxia Telangiectasia - genetics; Ataxia telangiectasia mutated protein; Ataxia Telangiectasia Mutated Proteins - genetics; ATM; Child; Child, Preschool; class switching recombination; Diagnosis; Diarrhea; Fever; Frameshift mutation; Genetic disorders; Genotype & phenotype; Genotypes; Humans; Immunodeficiency; Iran; Medicin och hälsovetenskap; Mutation; Patients; Phenotype; phenotype severity; Phenotypes; Radiosensitivity; Respiratory tract diseases; whole‐exome sequencing; Iran; ataxia-telangiectasia; phenotype severity; ATM; whole-exome sequencing; class switching recombination
• ISSN: 0905-6157; 1399-3038; 1399-3038
• DOI: 10.1111/pai.13461

Background Ataxia‐telangiectasia (A‐T) is a rare genetic disorder characterized by a distinct range of clinical manifestations, including progressive ataxia, immunodeficiency, and radiosensitivity. Methods 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. Results 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. Conclusion 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.