G6PD缺陷症基因型分析：一种新的错义突变

目的 对葡萄糖-6-磷酸脱氢酶(G6PD)缺陷症患者进行G6PD基因型分析,分析基因突变类型.方法 选取经G6PD活性测定确诊为G6PD缺陷症的49例患者和100名G6PD活性正常的体检者的全血标本,PCR和DNA测序法对G6PD基因外显子2～13进行序列分析.结果 49例G6PD缺陷症患者中,共发现12种错义突变,其中常见的三种为G6PD G1388A(26.5%)、G1376T(28.6%)和A95G(14.3%),此三类基因型患者G6PD活性仅为正常人群的5%～18%.临床主要表现为新生儿黄疸、进食蚕豆后发生急性溶血性贫血等.其余突变类型包括C1024T(4.1%)、C1225T(2.0%)、C1159T(2.0%)、G487A(4.1%)、G392T(4.1%)、G1160A(6.1%)、G871A/C1311T(4.1%)和C406T/C1311T(2.0%);在外显子7上发现了一种新的错义突变即G691C,该突变造成G6PD第231位丙氨酸(Ala)被脯氨酸(Pro)替代.正常对照标本未发现相同的基因改变.结论 G6PD基因G1388A、G1376T和A95G是G6PD缺陷症患者最常见的三种突变类型.新发现的G691C突变导致Ala231Pro,是引起红细胞G6PD活性降低,患者临床出现溶血症状的主要原因.

Analysis of glucose-6-phosphate dehydrogenase gene mutations: a novel missense mutation

Objective To analyse the types of glucose-6-phosphate dehydrogenase (G6PD) gene mutations in patients with G6PD deficiency. Methods The blood samples of 49 patients with G6PD deficiency and 100 normal subjects confirmed by G6PD activity detection were collected. Sequence analysis was performed on 12 exons from 2 to 13 by PCR and DNA sequencing. Results Twelve different missense G6PD mutations were detected, and the three most common mutations were G6PD G1388A (26.5%), G1376T (28.6%) and A95G (14.3%). The G6PD activity of these individuals was 5% to 18% of that of normal subjects. The clinical manifestations of these subjects were acute hemolytic anemia trigged by ingestion of fava bean and neonatal jaundice. The other mutations included C1024T (4.1%), C1225T (2.0%), C1159T (2.0%), G487A (4.1%), G392T (4.1%), G1160A (6.1%), G871A / C1311T (4.1%) and C 406T/C1311T (2.0%). A novel missense mutation (G691 C) in exon 7 of the G6PD gene predicting a single amino acid substitution, Ala231Pro was identified. The same gene mutations were not detected in samples of normal subjects. Conclusion G6PD gene G1388A, G1376T and A95G are the three most common types of G6PD gene mutations in patients with G6PD deficiency. A novel missense mutation G691C is found, which produces an Ala231Pro substitution and leads to significantly decreased G6PD activity in red blood cells.