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Research Article Free access | 10.1172/JCI106535

Hemoglobin Savannah (B6(24) β-glycine→valine): an unstable variant causing anemia with inclusion bodies

T. H. J. Huisman, Audrey K. Brown, G. D. Efremov, J. B. Wilson, Cecelia A. Reynolds, R. Uy, and Linda L. Smith

Laboratory of Protein Chemistry and the Department of Pediatrics, Medical College of Georgia, Augusta, Georgia 30902

Laboratory of Protein Chemistry and the Department of Biochemistry, Medical College of Georgia, Augusta, Georgia 30902

*

Deceased, 9 March 1970.

Find articles by Huisman, T. in: PubMed | Google Scholar

Laboratory of Protein Chemistry and the Department of Pediatrics, Medical College of Georgia, Augusta, Georgia 30902

Laboratory of Protein Chemistry and the Department of Biochemistry, Medical College of Georgia, Augusta, Georgia 30902

*

Deceased, 9 March 1970.

Find articles by Brown, A. in: PubMed | Google Scholar

Laboratory of Protein Chemistry and the Department of Pediatrics, Medical College of Georgia, Augusta, Georgia 30902

Laboratory of Protein Chemistry and the Department of Biochemistry, Medical College of Georgia, Augusta, Georgia 30902

*

Deceased, 9 March 1970.

Find articles by Efremov, G. in: PubMed | Google Scholar

Laboratory of Protein Chemistry and the Department of Pediatrics, Medical College of Georgia, Augusta, Georgia 30902

Laboratory of Protein Chemistry and the Department of Biochemistry, Medical College of Georgia, Augusta, Georgia 30902

*

Deceased, 9 March 1970.

Find articles by Wilson, J. in: PubMed | Google Scholar

Laboratory of Protein Chemistry and the Department of Pediatrics, Medical College of Georgia, Augusta, Georgia 30902

Laboratory of Protein Chemistry and the Department of Biochemistry, Medical College of Georgia, Augusta, Georgia 30902

*

Deceased, 9 March 1970.

Find articles by Reynolds, C. in: PubMed | Google Scholar

Laboratory of Protein Chemistry and the Department of Pediatrics, Medical College of Georgia, Augusta, Georgia 30902

Laboratory of Protein Chemistry and the Department of Biochemistry, Medical College of Georgia, Augusta, Georgia 30902

*

Deceased, 9 March 1970.

Find articles by Uy, R. in: PubMed | Google Scholar

Laboratory of Protein Chemistry and the Department of Pediatrics, Medical College of Georgia, Augusta, Georgia 30902

Laboratory of Protein Chemistry and the Department of Biochemistry, Medical College of Georgia, Augusta, Georgia 30902

*

Deceased, 9 March 1970.

Find articles by Smith, L. in: PubMed | Google Scholar

Published March 1, 1971 - More info

Published in Volume 50, Issue 3 on March 1, 1971
J Clin Invest. 1971;50(3):650–659. https://doi.org/10.1172/JCI106535.
© 1971 The American Society for Clinical Investigation
Published March 1, 1971 - Version history
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Abstract

An abnormal hemoglobin, termed Hb Savannah, was found in red cell hemolysate of a young Caucasian girl with severe hemolytic anemia. The presence of this unstable variant became evident when inclusion bodies appeared rapidly upon exposure of red cells to redox dyes and a large percentage of hemoglobin in hemolysate precipitated on warming to 65°C. Treatment of the hemoglobin with p-hydroxymercuribenzoate (PMB) caused a rapid dissociation into monomers; starch-gel electrophoresis of PMB-treated hemoglobin showed the presence of abnormal β-chains. Data from structural studies of isolated β-chains indicated substitution of a valyl residue for the normally occurring glycyl residue at position 24, which corresponds to helical residue B6. A similar substitution but with an arginine replacing the glycyl residue has been observed in Hb Riverdale-Bronx. The glycine to valine substitution will change the relationship of the B and the E helices which results in extensive conformational changes in the β-chain. This change presumably causes an increased dissociation of the hemoglobin molecule into dimers and probably monomers, and a decreased stability of the αβ-dimers. The hemoglobin abnormality may be the result of a fresh mutation because the abnormality is not present in the parents nor in any of the seven siblings.

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