β -Thalassemia Present in cis to a New β -Chain Structural Variant, Hb Vicksburg [β 75(E19)Leu→ 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, 3.4% HbA2, and 7.6% Hb Vicksburg, which had the electrophoretic and chromatographic properties of Hb A. Structural analysis of Hb Vicksburg demonstrated...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 78; no. 1; pp. 469 - 473 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences of the United States of America
01.01.1981
National Acad Sciences |
Subjects | |
Online Access | Get full text |
ISSN | 0027-8424 1091-6490 1091-6490 |
DOI | 10.1073/pnas.78.1.469 |
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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, 3.4% HbA2, 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 β 75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The α /non-α biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and β0-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 βVicksburgmRNA; in individuals with Hb St. Antoine (β 74 and β 75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of β 75, therefore, would not in itself appear to lead to diminished synthesis. There was a profound deficit of βVicksburgmRNA when measured by liquid hybridization analysis with β cDNA.. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for β+-thalassemia is present in cis to the structural mutation. |
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AbstractList | 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. 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, 3.4% HbA2, 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 β 75(E19), a new variant. Hb Vicksburg was neither unstable nor subject to posttranslational degradation. The α /non-α biosynthetic ratio was 2.6. Because the proband appeared to be a mixed heterozygote for Hb Vicksburg and β0-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 βVicksburgmRNA; in individuals with Hb St. Antoine (β 74 and β 75 deleted), the abnormal hemoglobin comprised 25% of the hemolysate in the simple heterozygote yet was unstable. Deletion of β 75, therefore, would not in itself appear to lead to diminished synthesis. There was a profound deficit of βVicksburgmRNA when measured by liquid hybridization analysis with β cDNA.. The most plausible explanation for the low output of Hb Vicksburg is that a mutation for β+-thalassemia is present in cis to the structural mutation. |
Author | Newman, Marsha V. Steinberg, Martin H. Morrison, W. Tully Iyer, Rathi Benz, Edward J. Adams, Junius G. |
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Snippet | 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, 3.4% HbA2,... 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,... |
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SubjectTerms | Amino acids Child Chromatography, Ion Exchange Complementary DNA Crossovers Electrophoresis Erythrocytes Fetal Hemoglobin - analysis Gels Genetic Linkage Globins - biosynthesis Globins - genetics Hemoglobin A2 - analysis Hemoglobins Hemoglobins - analysis Hemoglobins, Abnormal - analysis Hemoglobins, Abnormal - genetics Humans Male Messenger RNA Reticulocytes RNA RNA, Messenger - analysis Thalassemia Thalassemia - genetics |
Title | β -Thalassemia Present in cis to a New β -Chain Structural Variant, Hb Vicksburg [β 75(E19)Leu→ 0] |
URI | https://www.jstor.org/stable/10067 http://www.pnas.org/content/78/1/469.abstract https://www.ncbi.nlm.nih.gov/pubmed/6165992 https://pubmed.ncbi.nlm.nih.gov/PMC319075 https://www.ncbi.nlm.nih.gov/pmc/articles/319075 |
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