Clinical Manifestations and Genetic Findings in Three Patients with Chediak-Higashi Syndrome: Highlighting the Splice...

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.