Identification of the homologous beige and Chediak–Higashi syndrome genes (original) (raw)

• Letter
• Published: 18 July 1996
• Quan A. Nguyen1,2,
• Velizar T. Tchernev1,2,
• Jennifer A. Ashley3,
• John C. Detter1,2,
• Susan M. Blaydes1,2,
• Stephen J. Brandt4,
• Dipti Chotai5,
• Charles Hodgman5,
• Roberto C. E. Solari5,
• Michael Lovett3 &
• …
• Stephen F. Kingsmore1,2

Nature volume 382, pages 262–265 (1996)Cite this article

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A Correction to this article was published on 02 January 1997

Abstract

VESICULAR transport to and from the lysosome and late endosome is defective in patients with Chediak–Higashi syndrome (CHS) and in mutant beige (bg) mice1–4. CHS and bg cells have giant, perinuclear vesicles with characterises of late endosomes and lysosomes that arise from dysregulated homotypic fusion3–5. CHS and bg lysosomes also exhibit compartmental missorting of proteins, such as elastase, glucuronidase and cathepsin G2,3,6,7. Lyst, a candidate gene for bg, was identified by direct complementary DNA selection from a yeast artificial chromosome (YAC) clone containing a 650-kilobase segment of the _bg_-critical region on mouse chromosome 13. Lyst is disrupted by a 5-kilobase deletion in bg 11J mice, and Lyst messenger RNA is markedly reduced in bg 2J homozygotes. The homologous human gene, LYST, is highly conserved with mouse Lyst, and contains a frame-shift mutation at nucleotides 117–118 of the coding domain in a CHS patient. Thus bg mice and human CHS patients have homologous disorders associated with Lyst mutations. Lyst encodes a protein with a carboxy-terminal prenylation motif and multiple potential phosphorylation sites. Lyst protein is predicted to form extended helical domains, and has a region of sequence similar to stathmin, a coiled-coil phosphoprotein thought to act as a relay integrating cellular signal response coupling8–10.

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Authors and Affiliations

1. Departments of Medicine and Pathology,
   Maria D. F. S. Barbosa, Quan A. Nguyen, Velizar T. Tchernev, John C. Detter, Susan M. Blaydes & Stephen F. Kingsmore
2. Center for Mammalian Genetics, University of Florida, Gainesville, Florida, 32610, USA
   Maria D. F. S. Barbosa, Quan A. Nguyen, Velizar T. Tchernev, John C. Detter, Susan M. Blaydes & Stephen F. Kingsmore
3. Department of Biochemistry and the McDermott Center, The University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA
   Jennifer A. Ashley & Michael Lovett
4. Departments of Medicine and Cell Biology, Vanderbilt University, Nashville, Tennessee, 37232, USA
   Stephen J. Brandt
5. Cell Biology, Advanced Technologies and Informatics Units, Glaxo Wellcome Medicines Research Center, Stevenage, Hertfordshire, SG1 2NY, UK
   Dipti Chotai, Charles Hodgman & Roberto C. E. Solari

Authors

1. Maria D. F. S. Barbosa
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2. Quan A. Nguyen
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3. Velizar T. Tchernev
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4. Jennifer A. Ashley
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5. John C. Detter
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6. Susan M. Blaydes
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7. Stephen J. Brandt
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8. Dipti Chotai
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9. Charles Hodgman
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10. Roberto C. E. Solari
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11. Michael Lovett
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12. Stephen F. Kingsmore
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Barbosa, M., Nguyen, Q., Tchernev, V. et al. Identification of the homologous beige and Chediak–Higashi syndrome genes.Nature 382, 262–265 (1996). https://doi.org/10.1038/382262a0

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• Received: 10 May 1996
• Accepted: 20 June 1996
• Issue Date: 18 July 1996
• DOI: https://doi.org/10.1038/382262a0

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