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

1996; Nature Portfolio; Volume: 14; Issue: 3 Linguagem: Inglês

10.1038/ng1196-307

1546-1718

Deborah L. Nagle, Mohammad A. Karim, Elizabeth A. Woolf, Lisa Holmgren, Peer Bork, Donald J. Misumi, Sonja H. McGrail, Barry J. Dussault, Charles M. Perou, Raymond E. Boissy, Geoffrey M. Duyk, Richard A. Spritz, Karen J. Moore,

Immunodeficiency and Autoimmune Disorders

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.