Compensation, Training & Development, Organizational citizenship behavior (OCB) , Organizational commitment (ORC) , private healthcare sector in Bethlehem Palestine رسالة ماجستير

Abstract

Primary immunodeficiencies (PIDs) are genetic disorders that result in dysregulation of the immune system, causing a wide range of symptoms ranging from recurrent infections to autoimmunity and malignancy. Early detection of PIDs helps avoid complications and enables targeted therapies such as bone marrow transplantation. The Palestinian population is not only highly consanguineous but also underserved, meaning that disease-causing variants in PIDs are not well characterized. In this study, we investigated the genetic variants of 67 patients with PIDs from 54 families and did in-depth analysis of five selected cases. The patients had symptoms suggesting primary immunodeficiency, with some of them overlapping with immune dysregulation symptoms. Clinical characterization of patient’s symptoms was done for all patients. Exome or whole genome sequencing was done for the index in each family followed by deep analysis of the resulting data. The most common manifestations were recurrent infections and fever, while skin abnormalities were observed in 49% (33/67) of patients and 41% (28/67) of the patients had failure to thrive. The patients had variable laboratory testing results with White Blood Cell (WBCs) abnormalities seen in 52% (35/67), immunoglobulin levels abnormalities in 52% (35/67) and elevated inflammatory markers in 46% (31/67). Genetic diagnoses were identified in 17 families (31%). Additionally, three novel variants were found in new disease genes, and one known variant revealed a potentially new disease mechanism while, six patients had variants of uncertain significance identified in immune-related genes. Notably, none of these variants were detected in a diagnostic facility in Palestine. Eight patients found to have pathogenic variants in the MEFV gene, associated with the autoinflammatory disorder Familial Mediterranean Fever. Comprehensive analysis of the selected cases identified important variants in the following genes: ZNF341, RTEL1, DOCK11, IL36RN and TNFRSF13B. Our findings indicate that advanced genomic diagnostics and robust variant analysis are crucial for early detection and improving outcomes in PID patients, especially those with severe forms like SCID. It also highlights the importance of developing population-specific genetic screening programs and the need to equip the next generation of scientists with the variant’s interpretation skills required for advancing precision medicine in underserved populations.