Abstract:

Objective To explore the clinical characteristics and genetic features of Chediak-Higashi syndrome. Methods Trio whole-exome sequencing (trio-WES) was performed to identify the pathogenic gene variant. The clinical data of the child were summarized, and the clinical and genetic characteristics were analyzed. Results The patient, a 1-year and 7-month-old boy, presented to the dermatology department of the Children's Hospital of Fudan University with the chief complaints of pigmentation on the face and distal limbs, accompanied by gray hair for over one year. Trio-WES revealed compound heterozygous mutations in the LYST gene (c.2962C>T, c.10564+1dupG). The splicing site mutation (c.10564+1dupG) was a de novo variant. The inheritance pattern was consistent with autosomal recessive inheritance. A final diagnosis of Chediak-Higashi syndrome caused by LYST gene mutations was made. Conclusion Cases of Chediak-Higashi syndrome caused by LYST gene mutations are rarely reported. The variant combination identified in this case is previously unreported, which expands the genotype-phenotype spectrum of LYST gene defects and provides further data for understanding Chediak-Higashi syndrome. Precise diagnosis relies on molecular genetic testing. More cases need to be accumulated to further analyze the genotype-phenotype correlation and prognostic evaluation.

Key words: LYST gene, Chediak-Higashi syndrome, whole exome sequencing