Nagle D L, Karim M A, Woolf E A, Holmgren L, Bork P, Misumi D J, McGrail S H, Dussault B J, Perou C M, Boissy R E, Duyk G M, Spritz R A, Moore K J
Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
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.
切-东综合征（CHS）是一种罕见的常染色体隐性疾病，其特征为色素减退、伴有中性粒细胞减少的严重免疫缺陷以及缺乏自然杀伤（NK）细胞、出血倾向和神经学异常。大多数患者在儿童期死亡。CHS的标志是在多种细胞类型中出现巨大包涵体和细胞器，以及蛋白质向这些细胞器的分选缺陷。在米色小鼠（被认为是人类CHS的模型）中也出现了类似的异常。最近有两个研究小组报告了米色基因的鉴定结果，然而这两个cDNA完全不相似。在此我们描述了与小鼠米色基因同源的人类cDNA序列，鉴定了致病突变并澄清了先前报告中的差异。对CHS多肽的分析表明，其模块化结构与酵母液泡分选蛋白VPS15相似。
