Identification and mutation analysis of the complete gene for Chediak-Higashi syndrome

Nat Genet. 1996 Nov;14(3):307-11. doi: 10.1038/ng1196-307.


Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder characterized by hypopigmentation, severe immunologic deficiency with neutropenia and lack of natural killer (NK) cells, a bleeding tendency and neurologic abnormalities. Most patients die in childhood. The CHS hallmark is the occurrence of giant inclusion bodies and organelles in a variety of cell types, and protein sorting defects into these organelles. Similar abnormalities occur in the beige mouse, the proposed model for human CHS. Two groups have recently reported the identification of the beige gene, however the two cDNAs were not at all similar. Here we describe the sequence of a human cDNA homologous to mouse beige, identify pathologic mutations and clarify the discrepancies of the previous reports. Analysis of the CHS polypeptide demonstrates that its modular architecture is similar to the yeast vacuolar sorting protein, VPS15.

MeSH terms

  • Adult
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Chediak-Higashi Syndrome / genetics*
  • Cloning, Molecular
  • DNA Mutational Analysis*
  • Endosomal Sorting Complexes Required for Transport
  • Female
  • Homozygote
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Open Reading Frames
  • Protein Conformation
  • Protein-Serine-Threonine Kinases / genetics
  • Proteins / chemistry
  • Proteins / genetics*
  • Sequence Homology, Amino Acid
  • Vacuolar Sorting Protein VPS15
  • Vesicular Transport Proteins


  • Endosomal Sorting Complexes Required for Transport
  • Intracellular Signaling Peptides and Proteins
  • LYST protein, human
  • Lyst protein, mouse
  • Proteins
  • Vesicular Transport Proteins
  • PIK3R4 protein, human
  • Pik3r4 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Vacuolar Sorting Protein VPS15

Associated data

  • GENBANK/U67615