Tehran University of Medical Sciences Immunology and Genetics Journal 2645-4831 5 4 2022 12 22 141 148 EN Fawzia Takhari Clinical Research Development Unit of Akbar Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Hamid Ahanchian Allergy Research Center, School of medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Child Health Research Centre, University of Queensland, South Brisbane, Australia Nasrin Moazzen Subspecialist in Asthma and Allergy, Mashhad University of Medical Science, Mashhad, Iran Nafiseh Purbadakhshan Clinical Research Development Unit of Akbar Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Mohammad Hasan Aalami Clinical Research Development Unit of Akbar Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Rana Tafrishi Department of Allergy and Clinical Immunology, Ghaem hospital, Mashhad University of Medical Sciences, Mashhad, Iran Ehsan Ghayour Karimani Department of Genetics, Islamic Azad University of Mashhad, Mashhad, Iran Zahra Abbasi Shaye Clinical Research Development Unit of Akbar Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2024 03 07 2024 07 18 Background: The purpose of this study was genetic evaluation of patients suspected of immunodeficiency, without a definitive diagnosis, referred to the Immunodeficiency Clinic of Akbar Hospital in Mashhad in 2021-2022. Methods: In this study, patients suspected of immunodeficiency, without a definitive diagnosis, referred to an immunodeficiency clinic were included A complete clinical and paraclinical examination has been done by expert specialists and clinical geneticists. Blood samples were taken for genetic analysis using the Exome Sequencing technique followed by comprehensive bioinformatics analysis. Parents and healthy offspring were assessed for the candidate gene variants. Results: In this study, 185 patients were included; 58.56% of them were male; The average age of the participants was 9.28±5.40 years, and consanguineous marriage of parents was observed in 79.8 % of cases. Pneumonia with 33.51% was the most common clinical manifestation in patients with suspected immunodeficiency. In total, 41.14% of patients suffered from combined immunodeficiency, 26 .86% of them had defects of phagocyte number, function, or both; and 24% had predominantly antibody deficiencies. Hyper IgE syndrome was detected in 16% of patients, SCID and CGD each in 14.86% of patients, CVID in 12% of patients, and LAD in 7.43% of them. In 37.04% of the identified genes, there was a discrepancy between clinical and genetic diagnosis in patients. Conclusion: The most common clinical manifestation of patients suspected of primary immunodeficiency is pneumonia; therefore, patients who suffer from recurrent respiratory infections should be checked for genetic immunodeficiency. In this study, most patients were in the groups of immunodeficiencies affecting multiple cell types, defects of phagocyte number, function, or both; and predominantly antibody deficiencies, respectively. The most common diseases diagnosed were: Hyper IgE syndrome, SCID and CGD, CVID, and LAD. https://igj.tums.ac.ir/index.php/igj/article/view/135 https://igj.tums.ac.ir/index.php/igj/article/download/135/110