Background. Severe combined immunodeficiency (SCID) is a form of immunodeficiencies (PID), caused by molecular defects. These defects can restrict the development and function of lymphocytes. Early diagnosis and treatment of SCID can lead to disease-free survival. Objective. This study aims to investigate some of the possible underlying genetic defects in a group of Egyptian infants and children with clinical and immunological profiles suggestive of SCID. Methods. This study included eighty patients who showed clinical warning signs of immunodeficiency. Subjects were thoroughly examined clinically. Laboratory evaluation included immunoglobulins serum levels and flow cytometric assessment of immune cells. This testing showed an altered immune profile in thirty patients. They had decreased T and/or B lymphocytes or natural killer cells. DNA extraction was done for those cases. The coding regions of the RAG1 gene and RAG2 gene was investigated for hot spot mutations by sequencing technique guided by the patient clinical evaluation, inheritance pattern, immunophenotyping by flow cytometric analysis of lymphocyte subsets, and serum immunoglobulins level detection. Results. Results showed novel and previously reported variants (mutation, polymorphism), they were found in 18 cases which include variants in the RAG1 gene (E880K, A960A, H249R, S913R, K820R, V782G), and variants in the RAG2 gene (P501T, L514M, rs10836573, cDNA.2129A>T). Conclusions. To evaluate SCID patients completely; mutation gene analysis is highly required and recommended.
Keywords: PID; RAG gene; SCID; flow cytometry; genetic variants.