Molecular Genetics of Chediak–Higashi Syndrome

Abstract

Chediak–Higashi syndrome (CHS) is an autosomal recessive disorder associated with the formation of enlarged lysosomes and lysosome‐related organelles (LROs) clustered near the perinuclear region of cells. Affected vesicles include lysosomes, cytolytic granules, melanosomes and platelet dense granules. The enlarged vesicles give rise to decreased bacterial killing, partial albinism, defective wound repair, impaired coagulation and neurological problems. Patients succumb to untreated recurrent bacterial infections or a lymphoma‐like infiltration into the major organs of the body. Treatment for the disorder is prophylactic antibiotics followed by bone marrow transplant although pigmentation and neurological problems persist. The mutant gene, termed Lyst , responsible for CHS is present in all eukaryotes and model organisms have been utilised to try to determine the function of Lyst. The biochemical function of Lyst has not been resolved but Lyst has been proposed to be involved in regulating lysosome/LRO size by either controlling vesicle fusion or fission. Key Concepts: Chediak–Higashi syndrome (CHS) is a lethal disorder with patients succumbing to pathogen infections if not treated with antibiotics. CHS patients show multiorgan dysfunction due to enlarged lysosome‐related organelles in all cells of the body. Treatment for CHS is bone marrow transplant, although neurological problems remain. The mutant gene responsible for CHS is Lyst, a highly conserved gene present in all eukaryotes. Lyst is a member of a family of proteins, BEACH, involved in vesicle trafficking. Regulating lysosome/LRO size is important for normal cellular processes including pigmentation, coagulation, wound repair and immune function.