Clinical Manifestations,Immunological And Genetic Analysis Of 2 Case Of Chediak Higashi Syndrome

Objective: To analyze the clinical manifestations,immunological function and genetic mutation in 2 patients with Chediak-Higashi syndrome,to provide suggestions for diagnosis and differential diagnosis.In addition,to explore the function of neutrophils in patient with Chediak-Higashi syndrome.Methods:Two patients diagnosed as Chediak-Higashi syndrome who came to Children's Hospital of Chongqing Medical University from January 2018 to May 2018 were enrolled in the study.The clinical characteristics of these 2 patients were analyzed.The neutrophils from patients and healthy controls were stimulated with ionomycin,PMA,fMLP and WKYMVM,respectively to detect the production of reactive oxygen species.LYST gene mutations were detected by PCR high-throughput sequencing.Results:Both patients had typical manifestations of CHS.They had hypopigmentation of Skin and hair,immunodeficiency,Peroxidase-positive giant inclusions can be seen in leukocytes and other bone marrow precursors.P2 suffered hemophagocytic lymphohistiocytosis.The Chediak-Higashi syndrome is a rare primary immunodeficiency disease.However,there are a few studies concerning neutrophil function about this disease.We found that with the stimulation of ionomycin,the ROS produced by neutrophils in both two patients with CHS were significantly lower than that in the control groups.However with the stimulation of PMA,fMLP and WKYMVM,the ROS produced by neutrophils in the two patients hadn't obvious difference compared with the control groups.Through molecular genetic testing,P1 was found to have a compound heterozygous mutation of LYST gene(c.7207C>T and c.3556-1G>C).A compound heterozygous with mutation of LYST gene(c.985C>T and c.11268-1G>A)was detected in P2.Conclusion: The neutrophils in 2 patients diagnosed as CHS had obviously decreased production of reactive oxygen species under the stimulation of ionomycin,while the production of reactive oxygen species were basically normal under the stimulation of PMA,fMLP and WKYMVM,suggesting that the signaling producing reactive oxygen species under the stimulation of ionomycin was damaged in neutrophils of patients with CHS.This has great significance for further understanding of the process and mechanism of neutrophils against pathogens in CHS patients,also providing a new idea for the functional study of LYST.CHS can be diagnosed by typical clinical manifestations,Bone marrow cell smear,genetic testing and so on.