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 inProceedings of the National Academy of Sciences - PNAS Vol. 78; no. 1; pp. 469 - 473
Main Authors Adams, Junius G., Steinberg, Martin H., Newman, Marsha V., Morrison, W. Tully, Benz, Edward J., Iyer, Rathi
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences of the United States of America 01.01.1981
National Acad Sciences
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Online AccessGet full text
ISSN0027-8424
1091-6490
1091-6490
DOI10.1073/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.
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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StartPage 469
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]
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http://www.pnas.org/content/78/1/469.abstract
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