The spectrum of ATM gene mutations in Iranian patients with ataxia-telangiectasia.
ATM
ataxia-telangiectasia
class switching recombination
phenotype severity
whole-exome sequencing
Journal
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
ISSN: 1399-3038
Titre abrégé: Pediatr Allergy Immunol
Pays: England
ID NLM: 9106718
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
19
01
2021
received:
02
12
2020
accepted:
26
01
2021
pubmed:
7
2
2021
medline:
5
10
2021
entrez:
6
2
2021
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Substances chimiques
ATM protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1316-1326Informations de copyright
© 2021 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
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