Chediak-Higashi syndrome

Curr Opin Hematol. 2008 Jan;15(1):22-9. doi: 10.1097/MOH.0b013e3282f2bcce.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aleutian Mink Disease / genetics
  • Aleutian Mink Disease / pathology
  • Animals
  • Antibiotic Prophylaxis
  • Bone Marrow Transplantation
  • Chediak-Higashi Syndrome* / complications
  • Chediak-Higashi Syndrome* / genetics
  • Chediak-Higashi Syndrome* / pathology
  • Chediak-Higashi Syndrome* / surgery
  • Conserved Sequence
  • Disease Models, Animal
  • Disease Progression
  • Genes, Recessive
  • Hemorrhagic Disorders / etiology
  • Humans
  • Lymphoproliferative Disorders / etiology
  • Membrane Fusion / physiology
  • Mice
  • Mice, Mutant Strains
  • Mink
  • Multigene Family
  • Opportunistic Infections / etiology
  • Species Specificity
  • Transport Vesicles / metabolism
  • Transport Vesicles / pathology*
  • Vesicular Transport Proteins / deficiency*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / physiology

Substances

  • LYST protein, human
  • Vesicular Transport Proteins