Casimir C M, Bu-Ghanim H N, Rodaway A R, Bentley D L, Rowe P, Segal A W
Department of Medicine, Rayne Institute, University College London, United Kingdom.
Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2753-7. doi: 10.1073/pnas.88.7.2753.
Chronic granulomatous disease (CGD) is a rare inherited condition rendering neutrophils incapable of killing invading pathogens. This condition is due to the failure of a multicomponent microbicidal oxidase that normally yields a low-midpoint-potential b cytochrome (cytochrome b245). Although defects in the X chromosome-linked cytochrome account for the majority of CGD patients, as many as 30% of CGD cases are due to an autosomal recessive disease. Of these, greater than 90% have been shown to be defective in the synthesis of a 47-kDa cytosolic component of the oxidase. We demonstrate here in three unrelated cases of autosomal recessive CGD that the identical underlying molecular lesion is a dinucleotide deletion at a GTGT tandem repeat, corresponding to the acceptor site of the first intron-exon junction. Slippage of the DNA duplex at this site may contribute to the high frequency of defects in this gene.
慢性肉芽肿病（CGD）是一种罕见的遗传性疾病，使中性粒细胞无法杀死入侵的病原体。这种情况是由于一种多组分杀菌氧化酶功能异常，该氧化酶通常产生低中点电位的b型细胞色素（细胞色素b245）。尽管X染色体连锁细胞色素缺陷占大多数CGD患者，但多达30%的CGD病例是由常染色体隐性疾病引起的。其中，超过90%已被证明是氧化酶47 kDa胞质成分合成缺陷。我们在此证明，在三例无关的常染色体隐性CGD病例中，相同的潜在分子病变是GTGT串联重复序列处的二核苷酸缺失，对应于第一个内含子-外显子连接的受体位点。DNA双链在此位点的滑动可能导致该基因缺陷的高频率发生。
