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Open Access 01-01-2022 | Original Article

Genetic Risk Variants for Class Switching Recombination Defects in Ataxia-Telangiectasia Patients

Authors: Parisa Amirifar, Mahya Mehrmohamadi, Mohammad Reza Ranjouri, Seyed Mohammad Akrami, Nima Rezaei, Ali Saberi, Reza Yazdani, Hassan Abolhassani, Asghar Aghamohammadi

Published in: Journal of Clinical Immunology | Issue 1/2022

Abstract

Background

Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. A-T patients manifest considerable variability in clinical and immunological features, suggesting the presence of genetic modifying factors. A striking heterogeneity has been observed in class switching recombination (CSR) in A-T patients which cannot be explained by the severity of ATM mutations.

Methods

To investigate the cause of variable CSR in A-T patients, we applied whole-exome sequencing (WES) in 20 A-T patients consisting of 10 cases with CSR defect (CSR-D) and 10 controls with normal CSR (CSR-N). Comparative analyses on modifier variants found in the exomes of these two groups of patients were performed.

Results

For the first time, we identified some variants in the exomes of the CSR-D group that were significantly associated with antigen processing and presentation pathway. Moreover, in this group of patients, the variants in four genes involved in DNA double-strand breaks (DSB) repair signaling, in particular, XRCC3 were observed, suggesting an association with CSR defect.

Conclusion

Additional impact of certain variants, along with ATM mutations, may explain the heterogeneity in CSR defect phenotype among A-T patients. It can be concluded that genetic modulators play an important role in the course of A-T disease and its clinical severity.

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Title: Genetic Risk Variants for Class Switching Recombination Defects in Ataxia-Telangiectasia Patients
Authors: Parisa Amirifar
Mahya Mehrmohamadi
Mohammad Reza Ranjouri
Seyed Mohammad Akrami
Nima Rezaei
Ali Saberi
Reza Yazdani
Hassan Abolhassani
Asghar Aghamohammadi
Publication date: 01-01-2022
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 1/2022
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-021-01147-8

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Genetic Risk Variants for Class Switching Recombination Defects in Ataxia-Telangiectasia Patients

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