Abstract
Purpose
Early identification of inborn errors of immunity (IEIs) is crucial due to the significant risk of morbidity and mortality. This study aimed to describe the genetic causes, clinical features, and survival rate of IEIs in Omani patients.
Methods
A prospective study of all Omani patients evaluated for immunodeficiency was conducted over a 17-year period. Clinical features and diagnostic immunological findings were recorded. Targeted gene testing was performed in cases of obvious immunodeficiency. For cases with less conclusive phenotypes, a gene panel was performed, followed by whole-exome sequencing if necessary.
Results
A total of 185 patients were diagnosed with IEIs during the study period; of these, 60.5% were male. Mean ages at symptom onset and diagnosis were 30.0 and 50.5 months, respectively. Consanguinity and a family history of IEIs were present in 86.9% and 50.8%, respectively. Most patients presented with lower respiratory infections (65.9%), followed by growth and development manifestations (43.2%). Phagocytic defects were the most common cause of IEIs (31.9%), followed by combined immunodeficiency (21.1%). Overall, 109 of 132 patients (82.6%) who underwent genetic testing received a genetic diagnosis, while testing was inconclusive for the remaining 23 patients (17.4%). Among patients with established diagnoses, 37 genes and 44 variants were identified. Autosomal recessive inheritance was present in 81.7% of patients with gene defects. Several variants were novel. Intravenous immunoglobulin therapy was administered to 39.4% of patients and 21.6% received hematopoietic stem cell transplantation. The overall survival rate was 75.1%.
Conclusion
This study highlights the genetic causes of IEIs in Omani patients. This information may help in the early identification and management of the disease, thereby improving survival and quality of life.
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Data Availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on request.
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Acknowledgements
We would like to thank Prof. Raif Geha, Harvard University for his valuable review of the manuscript. We would like to thank all staff who participated in the care of these patients and all patients and their families for their trust.
Funding
Part of this study was funded by a Sultan Qaboos University research grant. No support was received during the preparation of this manuscript.
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The corresponding author was responsible for all aspects of the study conception and design as well as the preparation of the manuscript for publication. SZ & MR performed targeted gene sequencing and analysis; DD supervised the targeted gene sequence and analysis; SN and NS participated in clinical care and family support; KA performed genetic counseling; ZB, KD, FM, AS, and AM supervised panel gene testing and analysis of panel and whole-exome sequencing.
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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Medical Research and Ethics Committee of the College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
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Al-Tamemi, S., Al-Zadjali, S., Bruwer, Z. et al. Genetic Causes, Clinical Features, and Survival of Underlying Inborn Errors of Immunity in Omani Patients: a Single-Center Study. J Clin Immunol 43, 452–465 (2023). https://doi.org/10.1007/s10875-022-01394-3
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DOI: https://doi.org/10.1007/s10875-022-01394-3