de Boer Martin, Tzur Shay, van Leeuwen Karin, Dencher Paula C D, Skorecki Karl, Wolach Baruch, Gavrieli Ronit, Nasidze Ivane, Stoneking Mark, Tanck Michael W T, Roos Dirk
Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Dept. of Nephrology and Molecular Medicine, Rappaport Faculty of Medicine and Research Institute, Technion, and Rambam Medical Center, Haifa, Israel.
Blood Cells Mol Dis. 2015 Dec;55(4):320-7. doi: 10.1016/j.bcmd.2015.07.014. Epub 2015 Jul 23.
Chronic granulomatous disease (CGD) is a rare congenital immune deficiency caused by mutations in any of the five genes encoding NADPH oxidase subunits. One of these genes is NCF1, encoding the p47(phox) protein. A group of 39 patients, 14 of whom are of Kavkazi Jewish descent, was investigated for a founder effect for the mutation c.579G>A (p.Trp193Ter) in NCF1. We analyzed various genetic markers in the NCF1 region, including two single nucleotide polymorphisms (SNPs) in NCF1 and two short tandem repeats (STRs) located near NCF1. Most patients were homozygous for the c.579G>A mutation, but three patients were hemizygotes, with a deletion of NCF1 on the other allele, and three patients were compound heterozygotes with another mutation in NCF1. All Kavkazi Jewish patients had a c.295G_c.345T SNP combination in NCF1 and shared a common number of repeats in STR3. In addition, 90% of the Kavkazi Jewish patients shared a common number of repeats in STR1. This uniformity indicates that the c.579G>A mutation in NCF1 was introduced some 1200-2300 years ago in the Kavkazi Jewish population. Variation amongst the other investigated populations from the Middle East indicates that this mutation exists in these non-Kavkazi populations already for more than 5000 years.
慢性肉芽肿病（CGD）是一种罕见的先天性免疫缺陷病，由编码NADPH氧化酶亚基的五个基因中任何一个发生突变所致。其中一个基因是NCF1，编码p47(phox)蛋白。对一组39名患者进行了研究，其中14名患者为卡兹犹太人后裔，以调查NCF1基因中c.579G>A（p.Trp193Ter）突变的奠基者效应。我们分析了NCF1区域的各种遗传标记，包括NCF1中的两个单核苷酸多态性（SNP）和位于NCF1附近的两个短串联重复序列（STR）。大多数患者的c.579G>A突变是纯合子，但有三名患者是半合子，另一个等位基因上的NCF1发生了缺失，还有三名患者是复合杂合子，NCF1中有另一个突变。所有卡兹犹太人患者在NCF1中都有一个c.295G_c.345T SNP组合，并且在STR3中共享相同数量的重复序列。此外，90%的卡兹犹太人患者在STR1中共享相同数量的重复序列。这种一致性表明，NCF1中的c.579G>A突变是在大约1200 - 2300年前引入卡兹犹太人群体的。来自中东的其他被调查人群之间的差异表明，这种突变在这些非卡兹人群中已经存在了5000多年。
