beta-Thalassemia present in cis to a new beta-chain structural variant, Hb Vicksburg [beta 75 (E19)Leu leads to 0].

Abstract

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.

• Authors: J G Adams 3rd, M H Steinberg, M V Newman, W T Morrison, E J Benz Jr, R Iyer
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 78 Issue 1 Pg. 469-73 (Jan 1981) ISSN: 0027-8424 [Print] United States
• PMID: 6165992 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hemoglobins
• Hemoglobins, Abnormal
• RNA, Messenger
• hemoglobin Vicksburg
• Globins
• Hemoglobin A2
• Fetal Hemoglobin

Topics

• Child
• Chromatography, Ion Exchange
• Electrophoresis
• Fetal Hemoglobin (analysis)
• Genetic Linkage
• Globins (biosynthesis, genetics)
• Hemoglobin A2 (analysis)
• Hemoglobins (analysis)
• Hemoglobins, Abnormal (analysis, genetics)
• Humans
• Male
• RNA, Messenger (analysis)
• Thalassemia (genetics)