Clinical Manifestations and Genetic Findings in Three Patients with Chediak-Higashi Syndrome: Highlighting the Splice Site Variants
Abstract
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.
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BibTeX
@article{tajik2026clinical,
title = {{Clinical Manifestations and Genetic Findings in Three Patients with Chediak-Higashi Syndrome: Highlighting the Splice Site Variants}},
author = {Shaghayegh Tajik and Anne Molitor and Zahra Alizadeh and Mohammad Reza Fazlollahi and Raphaël Carapito and Maryam Akbari and Mohsen Badalzadeh and Massoud Houshmand and Mostafa Moin and Seiamak Bahram and Zahra Pourpak},
journal = {Iranian Journal of Allergy, Asthma and Immunology},
year = {2026},
month = jun,
doi = {10.18502/ijaai.v25i4.21743},
url = {https://univoak.hal.science/hal-05750418v1},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Clinical Manifestations and Genetic Findings in Three Patients with Chediak-Higashi Syndrome: Highlighting the Splice Site Variants
AU - Shaghayegh Tajik
AU - Anne Molitor
AU - Zahra Alizadeh
AU - Mohammad Reza Fazlollahi
AU - Raphaël Carapito
AU - Maryam Akbari
AU - Mohsen Badalzadeh
AU - Massoud Houshmand
AU - Mostafa Moin
AU - Seiamak Bahram
AU - Zahra Pourpak
PY - 2026
DA - 2026/06/14
JO - Iranian Journal of Allergy, Asthma and Immunology
DO - 10.18502/ijaai.v25i4.21743
UR - https://univoak.hal.science/hal-05750418v1
AB - 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.
SN - 1735-1502
SN - 1735-5249
ER -