Genetic Testing in Egyptian Patients with Inborn Errors of Immunity: a Single-Center Experience
Rabab E El Hawary1, Safa S Meshaal2, Dalia S Abd Elaziz3
1Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. rabab_elhawary@cu.edu.eg.
Journal of Clinical Immunology
|April 28, 2022
Summary
Genetic testing for inborn errors of immunity (IEI) in Egypt identified 72 genes with mutations, primarily RAG1/2. This study adapted molecular diagnostics for resource-limited settings, aiding genetic counseling and treatment decisions.
Area of Science:
- Immunology
- Genetics
- Molecular Diagnostics
Background:
- Inborn errors of immunity (IEI) are diverse genetic disorders with varying prevalence across populations.
- Egypt faces challenges in genetic diagnosis of IEI due to financial constraints.
- This study addresses the need to characterize the genetic landscape of IEI in Egypt.
Purpose of the Study:
- To determine the genetic spectrum of IEI patients in Egypt.
- To adapt and implement molecular diagnostic methods in a resource-limited environment.
- To provide a framework for genetic diagnosis and counseling for IEI in similar settings.
Main Methods:
- Analysis of genetic material from 504 patients, with diagnoses confirmed in 282.
- Utilized Sanger sequencing, targeted next-generation sequencing (NGS), and whole-exome sequencing (WES) based on clinical presentation and test availability.
- Focused on mutational analysis to identify causative variants.
Main Results:
- Detected 194 variants across 72 genes, with RAG1/2, DOCK8, CYBA, LRBA, NCF1, and JAK3 being the most frequently implicated.
- Autosomal recessive inheritance was predominant (82.6%), followed by X-linked (11.3%) and autosomal dominant (6.4%).
- The high prevalence of autosomal recessive inheritance reflects the impact of consanguinity.
Conclusions:
- A combined approach of Sanger sequencing and NGS/WES is effective for IEI diagnosis in resource-limited settings.
- Molecular testing validates less expensive laboratory techniques, facilitating definitive diagnoses.
- Accurate genetic diagnosis is crucial for informed genetic counseling and therapeutic decisions, including stem cell transplantation and gene therapy.
