Adams J G, Steinberg M H, Newman M V, Morrison W T, Benz E J, Iyer R
Proc Natl Acad Sci U S A. 1981 Jan;78(1):469-73. doi: 10.1073/pnas.78.1.469.
Hemoglobin Vicksburg was discovered in a 6-year-old Black boy who had been anemic since infancy. Examination of his hemolysate revealed 87.5% Hb F, 2.4% Hb A2, and 7.6% Hb Vicksburg, which had the electrophoretic and chromatographic properties of Hb A. Structural analysis of Hb Vicksburg demonstrated a deletion of leucine at beta 75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The alpha/non-alpha biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and beta 0-thalassemia, Hb Vicksburg should have comprised the major portion of the hemolysate. Thus, Hb Vicksburg was synthesized at a rate considerably lower than would be expected on the basis of gene dosage. There was no reason to suspect abnormal translation of beta Vicksburg mRNA; in individuals with Hb St. Antoine (beta 74 and beta 75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of beta 75, therefore, would not in itself appear to lead to diminished synthesis. There was a profound deficit of beta Vicksburg mRNA when measured by liquid hybridization analysis with beta cDNA. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for beta +-thalassemia is present in cis to the structural mutation.
维克斯堡血红蛋白是在一名自婴儿期就贫血的6岁黑人男孩身上发现的。对其溶血产物的检测显示，胎儿血红蛋白（Hb F）占87.5%，血红蛋白A2（Hb A2）占2.4%，维克斯堡血红蛋白（Hb Vicksburg）占7.6%，Hb Vicksburg具有Hb A的电泳和色谱特性。对Hb Vicksburg的结构分析表明，其β链第75位（E19）的亮氨酸缺失，这是一种新的变体。Hb Vicksburg既不稳定，也不受翻译后降解的影响。α/非α生物合成比率为2.6。由于先证者似乎是Hb Vicksburg和β0地中海贫血的混合杂合子，Hb Vicksburg应该占溶血产物的主要部分。因此，Hb Vicksburg的合成速率明显低于基于基因剂量预期的速率。没有理由怀疑β维克斯堡mRNA的翻译异常；在患有圣安托万血红蛋白（β74和β75缺失）的个体中，这种异常血红蛋白在单纯杂合子的溶血产物中占25%，但不稳定。因此，β75的缺失本身似乎不会导致合成减少。通过与β cDNA的液相杂交分析测量，β维克斯堡mRNA严重缺乏。Hb Vicksburg产量低最合理的解释是，在结构突变的顺式位置存在β +-地中海贫血突变。
