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

被引:379
作者
Nagle, DL
Karim, MA
Woolf, EA
Holmgren, L
Bork, P
Misumi, DJ
McGrail, SH
Dussault, BJ
Perou, CM
Boissy, RE
Duyk, GM
Spritz, RA
Moore, KJ
机构
[1] MILLENNIUM PHARMACEUT INC,CAMBRIDGE,MA 02139
[2] UNIV WISCONSIN,DEPT MED GENET,MADISON,WI 53706
[3] UNIV WISCONSIN,DEPT PEDIAT,MADISON,WI 53706
[4] EUROPEAN MOL BIOL LABS,HEIDELBERG,GERMANY
[5] MAX DELBRUCK CTR MOL MED,BERLIN,GERMANY
[6] UNIV UTAH,SCH MED,DEPT PATHOL,DIV CELL BIOL & IMMUNOL,SALT LAKE CITY,UT 84132
[7] UNIV CINCINNATI,COLL MED,DEPT DERMATOL,CINCINNATI,OH 45267
关键词
D O I
10.1038/ng1196-307
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 1-4. 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 5-8. Similar abnormalities occur in the beige mouse 6,7, 9-13, the proposed model for human CHS. Two groups have recently reported the identification of the beige gene 14,15, 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 sortina protein. VPS15.
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收藏
页码:307 / 311
页数:5
相关论文
共 37 条
[31]  
STEIN L, 1995, UNPUB
[32]  
STEINBRINCK W, 1948, DEUT ARCH KLIN MED, V193, P577
[33]  
SWANK RT, 1978, AM J PATHOL, V92, P755
[34]   THE ORIGIN AND FATE OF LARGE DENSE BODIES IN BEIGE MOUSE FIBROBLASTS - LYSOSOMAL FUSION AND EXOCYTOSIS [J].
WILLINGHAM, MC ;
SPICER, SS ;
VINCENT, RA .
EXPERIMENTAL CELL RESEARCH, 1981, 136 (01) :157-168
[35]  
Wootton JC, 1996, METHOD ENZYMOL, V266, P554
[36]  
ZHAO HQ, 1994, LAB INVEST, V71, P25
[37]   TOR KINASE DOMAINS ARE REQUIRED FOR 2 DISTINCT FUNCTIONS, ONLY ONE OF WHICH IS INHIBITED BY RAPAMYCIN [J].
ZHENG, XF ;
FIORENTINO, D ;
CHEN, J ;
CRABTREE, GR ;
SCHREIBER, SL .
CELL, 1995, 82 (01) :121-130