Karim M A, Nagle D L, Kandil H H, Bürger J, Moore K J, Spritz R A
Department of Medical Genetics, University of Wisconsin, Madison 53706, USA.
Hum Mol Genet. 1997 Jul;6(7):1087-9. doi: 10.1093/hmg/6.7.1087.
Chediak-Higashi syndrome (CHS) is a rare, usually fatal, autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, progressive neurologic dysfunction and a bleeding diathesis. The hallmark of CHS is giant organelles and giant granules in many different cell types, most likely the result of defective trafficking of specific organellar and granular proteins necessary for the normal genesis, structure or function of these cytoplasmic components. The CHS1 gene has recently been identified and shown to be homologous to the beige locus of the mouse; however, there has been disagreement as to the length of the functional CHS1 mRNA and protein. Here we report homozygous CHS1 gene mutations in two of the original probands we used to map the gene to 1q42-q44. One of these, a frameshift at codon 3197, supports our assertion that the functional CHS protein is a predicted 3801 amino acid polypeptide encoded by a 13.5 kb mRNA.
切迪阿克-东综合征（CHS）是一种罕见的、通常致命的常染色体隐性疾病，其特征为严重的免疫缺陷、色素沉着减少、进行性神经功能障碍和出血倾向。CHS的标志是许多不同细胞类型中存在巨大细胞器和巨大颗粒，这很可能是特定细胞器和颗粒蛋白运输缺陷的结果，而这些蛋白对于这些细胞质成分的正常生成、结构或功能是必需的。CHS1基因最近已被鉴定出来，并显示与小鼠的米色基因座同源；然而，关于功能性CHS1 mRNA和蛋白质的长度存在分歧。在此，我们报告了在最初用于将该基因定位于1q42-q44的两名先证者中发现的纯合CHS1基因突变。其中一个是第3197位密码子处的移码突变，这支持了我们的论断，即功能性CHS蛋白是由一个13.5 kb mRNA编码的预测为3801个氨基酸的多肽。
