Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 02 04 1 7 Shaghayegh Tajik Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Children’s Medical Center Hospital, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran Anne Molitor 0000-0003-1646-2325 Zahra Alizadeh Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Children’s Medical Center Hospital, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran Mohammad Reza Fazlollahi Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Children’s Medical Center Hospital, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran Raphael Carapito Laboratoire d'ImmunoRhumatologie Moléculaire, plateforme GENOMAX, INSERM UMR_S 1109, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Institut Thématique Interdisciplinaire TRANSPLANTEX NG, Université de Strasbourg, Strasbourg, France AND Service d'Immunologie Biologique, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Strasbourg, France Maryam Akbari Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran Mohsen Badalzadeh Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Children’s Medical Center Hospital, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran Massoud Houshmand Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran Mostafa Moin Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Children’s Medical Center Hospital, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran Seiamak Bahram 0000-0002-6928-9952 Zahra Pourpak Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Children’s Medical Center Hospital, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran 2025 08 19 2025 09 24 Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunodeficiency, partial albinism, recurrent infections, and progressive neurologic dysfunction. Unless patients undergo successful hematopoietic cell transplantation (HCT), a majority of them die during childhood because of an accelerated phase of immune dysfunction and hemophagocytic lymphohistiocytosis (HLH). Herein, we aim to describe the laboratory diagnosis, clinical manifestations, and genetic findings in three patients with CHS. Three patients with partial albinism associated with CHS were included in this study. Immunological screening tests were done. Leukocyte granules in peripheral blood smear (PBS) and hair shafts were examined. Subsequently, genetic analyses were performed by Whole Exome Sequencing (WES) followed by Sanger sequencing for all patients and their parents. Initial immunology screening tests were within normal limits. Light microscopy studies of patients’ PBS showed giant granules in the leukocyte cytoplasm. Furthermore, there were evenly distributed melanin granules in the patients' hair shafts. Variant analysis of the LYST gene identified three splicing site defects: one known variant, c.7060-1G>A in intron 24, and two novel variants, c.2363+2T>C in intron 5, and c.10702-3A>G in intron 47. Hair shaft assay and PBS are rapid and suitable tests in early diagnosis and differentiation in CHS patients. WES results revealed 2 novel splice site variants that might contribute to earlier and more accurate diagnosis. This facilitates early enrolment of CHS patients in the HCT protocol-the optimal treatment path-and enables prenatal diagnosis for affected families. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4555 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4555/2293