Hsia Y E, Miyakawa F, Baltazar J, Ching N S, Yuen J, Westwood B, Beutler E
Department of Genetics and Pediatrics, John A. Burns School of Medicine, University of Hawaii, Honolulu 96822.
Hum Genet. 1993 Nov;92(5):470-6. doi: 10.1007/BF00216453.
In a Hawaii Hereditary Anemia Screening Project, 4,984 participants were tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency by a filter paper blood spot fluorescence test. Abnormal samples and suspected heterozygotes were checked by quantitative G6PD assay (normal 4.5 to 14 units/g Hb). G6PD was deficient (< 1.5 units/g Hb) in 188 of 2,155 males; 7 other males had low activity (1.5 to 2.8 units/g Hb). The gene frequency, estimated from males after excluding referred and related cases, was 0.037 for Chinese, 0.134 for Filipinos, and 0.203 for Laotians. Among 2,829 females tested, family data showed 111 females were obliged to be at least heterozygous, regardless of G6PD activity, and 43 others had low G6PD activity. Most heterozygotes probably remained undetected by G6PD screening. In 28 females, activity was under 10%; in another 9 females, activity was < 1.5 units/g Hb. Since only 25 homozygotes would be predicted, this apparent excess of females with deficient activity could be due to unequal X-inactivation in some heterozygotes. DNA analysis by polymerase chain reaction amplification and special analytic procedures revealed 10 different missense mutations in 75 males. The nucleotide 835 A-->T and 1360 C-->T transitions were first detected in this Hawaiian Project; we found that the nucleotide 1360 mutation was the most common cause of G6PD deficiency in Filipinos. This is the first report of G6PD screening and analysis of molecular G6PD mutations in Filipino and Laotian populations.
在夏威夷遗传性贫血筛查项目中,4984名参与者通过滤纸血斑荧光试验检测葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症。异常样本和疑似杂合子通过定量G6PD测定法(正常范围为4.5至14单位/克血红蛋白)进行检查。在2155名男性中,188人G6PD缺乏(<1.5单位/克血红蛋白);另外7名男性活性较低(1.5至2.8单位/克血红蛋白)。排除转诊和相关病例后,从男性中估计的基因频率,中国人为0.037,菲律宾人为0.134,老挝人为0.203。在接受检测的2829名女性中,家族数据显示,无论G6PD活性如何,有111名女性必定至少为杂合子,另外43名女性G6PD活性较低。大多数杂合子可能未被G6PD筛查检测到。28名女性的活性低于10%;另有9名女性的活性<1.5单位/克血红蛋白。由于预计只有25名纯合子,这种活性缺乏的女性明显过多可能是由于一些杂合子中X染色体失活不均等所致。通过聚合酶链反应扩增和特殊分析程序进行的DNA分析在75名男性中发现了10种不同的错义突变。核苷酸835 A→T和1360 C→T转换首次在这个夏威夷项目中被检测到;我们发现核苷酸1360突变是菲律宾人G6PD缺乏的最常见原因。这是关于菲律宾人和老挝人群体中G6PD筛查及分子G6PD突变分析的首份报告。