Hirono A, Fujii H, Miwa S
Okinaka Memorial Institute for Medical Research; the Department of Blood Transfusion Medicine, Tokyo Women's Medical College, Japan.
Blood. 1995 Feb 15;85(4):1118-21.
Among over 50 distinct mutations causing glucose-6-phosphate dehydrogenase (G6PD) deficiency, only two deletion mutations have so far been reported. Using nonradioisotopic single-strand conformation polymorphism analysis, we found two additional deletion mutations in two Japanese G6PD-deficient patients with nonspherocytic hemolytic anemia. Case no. 1 had a 3-nucleotide deletion in exon 6 predicting a deletion of a serine at amino acid 188 or 189, which caused a class 1 variant G6PD Tsukui. Case no. 2 had a 3-nucleotide deletion in exon 5 predicting a deletion of a lysine at residue 95, which caused a class 2 variant G6PD Urayasu. The 188th serine, which might be deleted in G6PD Tsukui, is located close to the putative G6P binding site. The 188th serine is also involved in the amino acid substitution in G6PD Mediterranean, but the kinetics of these two variants are totally different. The residue with an amino acid deletion in G6PD Urayasu was distant from the substrate binding sites and was located in a region with low sequence homology among species. The different properties of variants having mutations in exons 5 and 6 suggest that these two exons code distinct functional domains of the enzyme.
在导致葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症的50多种不同突变中，迄今为止仅报道了两种缺失突变。我们使用非放射性单链构象多态性分析，在两名患有非球形细胞溶血性贫血的日本G6PD缺乏症患者中发现了另外两种缺失突变。病例1在外显子6中有一个3核苷酸缺失，预测在氨基酸188或189处缺失一个丝氨酸，这导致了1类变体G6PD津久井。病例2在外显子5中有一个3核苷酸缺失，预测在第95位残基处缺失一个赖氨酸，这导致了2类变体G6PD浦安。在G6PD津久井中可能缺失的第188位丝氨酸靠近假定的G6P结合位点。第188位丝氨酸也参与了G6PD地中海型中的氨基酸取代，但这两种变体的动力学完全不同。G6PD浦安中氨基酸缺失的残基距离底物结合位点较远，位于物种间序列同源性较低的区域。外显子5和6中具有突变的变体的不同特性表明，这两个外显子编码该酶不同的功能结构域。
