Chediak-Higashi syndrome.
OBJECTIVE
Chediak-Higashi syndrome, a rare autosomal recessive disorder, was described over 50 years ago. Patients show hypopigmentation, recurrent infections, mild coagulation defects and varying neurologic problems. Treatment is bone marrow transplant, which is effective in treating the hematologic and immune defects, however the neurologic problems persist. The CHS1/LYST gene was identified over 10 years ago and homologous CHS1/LYST genes are present in all eukaryotes. This review will discuss the advances made in understanding the clinical aspects of the syndrome and the function of CHS1/LYST/Beige.


RESULTS
Clinical reports of Chediak-Higashi syndrome have identified mutations throughout the CHS1/LYST gene. The nature of the mutation can be a predictor of the severity of the disease. Over the past decade the CHS1/LYST family of proteins has been analyzed using model organisms, two-hybrid analysis, overexpression phenotypes and dominant negatives. These studies suggest that the CHS1/LYST protein is involved in either vesicle fusion or fission.


CONCLUSIONS
Although CHS is a rare disease, the Chediak-like family of proteins is providing insight into the regulation of vesicle trafficking. Understanding the basic mechanisms that govern vesicle trafficking will provide essential information regarding how loss of CHS1/LYST affects hematologic, immunologic and neurologic processes.
Department of Pathology, University of Utah School of Medicine, 30 N. 1900 E., Salt Lake City, UT 84132, USA.
Jerry
J
Kaplan
Ivana
I
De Domenico
Diane McVey
DM
Ward
D000453:Aleutian Mink Disease / Q000235:genetics / Q000473:pathology; D000818:Animals; D019072:Antibiotic Prophylaxis; D016026:Bone Marrow Transplantation; D002609:Chediak-Higashi Syndrome / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000601:surgery; D017124:Conserved Sequence; D004195:Disease Models, Animal; D018450:Disease Progression; D005808:Genes, Recessive; D006474:Hemorrhagic Disorders / Q000209:etiology; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000209:etiology; D008561:Membrane Fusion / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008907:Mink; D005810:Multigene Family; D009894:Opportunistic Infections / Q000209:etiology; D013045:Species Specificity; D022161:Transport Vesicles / Q000378:metabolism / Q000473:pathology*; D033921:Vesicular Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
C102161:LYST protein, human; D033921:Vesicular Transport Proteins