Jendrossek V, Ritzel A, Neubauer B, Heyden S, Gahr M
Universitätskinderklinik Göttingen, Germany.
Eur J Haematol. 1997 Feb;58(2):78-85. doi: 10.1111/j.1600-0609.1997.tb00928.x.
In an adult patient suffering from X-linked chronic granulomatous disease (X-CGD) with residual activity of the NADPH-oxidase we found an unusual biochemical constellation with a defective gp91-phox gene. As shown by Western blot using a specific antibody the gp91-phox protein was normal in PMN. However, NADPH-oxidase activity was reduced and no heme spectrum was detectable. By Southern blot and RFLP analysis of genomic DNA a larger defect within the gp91-phox gene was excluded. Sequencing of the gp91-phox cDNA revealed an in-frame deletion of a TTC triplet in exon VI of the gp91-phox gene. This mutation indicates the loss of one amino acid (phenylalanine 215 or 216) in the gp91-phox protein. Sequencing of genomic DNA from the heterozygous daughter of the propositus confirmed this mutation. The absence of a functional cytochrome b558-spectrum in granulocytes of the patient suggests an involvement of the phenylalanine 216 area in heme binding by gp91 phox. This is the first mutation described in a X-CGD patient with absence of a functional cytochrome b558-spectrum but with detectable gp91-phox protein and residual NADPH-oxidase activity.
在一名患有X连锁慢性肉芽肿病（X-CGD）且NADPH氧化酶有残余活性的成年患者中，我们发现了一种不寻常的生化情况，其gp91-phox基因存在缺陷。使用特异性抗体进行的蛋白质印迹分析显示，中性粒细胞中的gp91-phox蛋白正常。然而，NADPH氧化酶活性降低，且未检测到血红素光谱。通过对基因组DNA进行Southern印迹和限制性片段长度多态性（RFLP）分析，排除了gp91-phox基因内更大的缺陷。对gp91-phox cDNA进行测序发现，gp91-phox基因外显子VI中有一个TTC三联体的框内缺失。该突变表明gp91-phox蛋白中缺失了一个氨基酸（苯丙氨酸215或216）。对先证者杂合子女儿的基因组DNA进行测序证实了这一突变。患者粒细胞中缺乏功能性细胞色素b558光谱，提示苯丙氨酸216区域参与了gp91 phox与血红素的结合。这是首次在一名X-CGD患者中描述的突变，该患者缺乏功能性细胞色素b558光谱，但可检测到gp91-phox蛋白和残余的NADPH氧化酶活性。
