beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0].
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.
D002648:Child; D002852:Chromatography, Ion Exchange; D004586:Electrophoresis; D005319:Fetal Hemoglobin / Q000032:analysis; D008040:Genetic Linkage; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006443:Hemoglobin A2 / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D013789:Thalassemia / Q000235:genetics*
D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; C030450:hemoglobin Vicksburg; D005914:Globins; D006443:Hemoglobin A2; D005319:Fetal Hemoglobin