Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI107356

Hemoglobin Abraham Lincoln, β32 (B14) Leucine → Proline AN UNSTABLE VARIANT PRODUCING SEVERE HEMOLYTIC DISEASE

George R. Honig, David Green, Mir Shamsuddin, Loyda N. Vida, R. George Mason, David J. Gnarra, and Helen S. Maurer

Department of Pediatrics, and the Sickle Cell Center, The Abraham Lincoln School of Medicine, University of Illinois, Chicago, Illinois 60612

Hematology Section, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611

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

Department of Pediatrics, and the Sickle Cell Center, The Abraham Lincoln School of Medicine, University of Illinois, Chicago, Illinois 60612

Hematology Section, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611

Find articles by Green, D. in: PubMed | Google Scholar

Department of Pediatrics, and the Sickle Cell Center, The Abraham Lincoln School of Medicine, University of Illinois, Chicago, Illinois 60612

Hematology Section, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611

Find articles by Shamsuddin, M. in: PubMed | Google Scholar

Department of Pediatrics, and the Sickle Cell Center, The Abraham Lincoln School of Medicine, University of Illinois, Chicago, Illinois 60612

Hematology Section, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611

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

Department of Pediatrics, and the Sickle Cell Center, The Abraham Lincoln School of Medicine, University of Illinois, Chicago, Illinois 60612

Hematology Section, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611

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

Department of Pediatrics, and the Sickle Cell Center, The Abraham Lincoln School of Medicine, University of Illinois, Chicago, Illinois 60612

Hematology Section, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611

Find articles by Gnarra, D. in: PubMed | Google Scholar

Department of Pediatrics, and the Sickle Cell Center, The Abraham Lincoln School of Medicine, University of Illinois, Chicago, Illinois 60612

Hematology Section, Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611

Find articles by Maurer, H. in: PubMed | Google Scholar

Published July 1, 1973 - More info

Published in Volume 52, Issue 7 on July 1, 1973
J Clin Invest. 1973;52(7):1746–1755. https://doi.org/10.1172/JCI107356.
© 1973 The American Society for Clinical Investigation
Published July 1, 1973 - Version history
View PDF
Abstract

An unstable hemoglobin variant was identified in a Negro woman with hemolytic anemia since infancy. A splenectomy had been performed when the patient was a child. The anemia was accompanied by erythrocyte inclusion bodies and excretion of darkly pigmented urine. Neither parent of the proposita demonstrated any hematologic abnormality, and it appeared that this hemoglobin variant arose as a new mutation. Erythrocyte survival in the patient was greatly reduced: the erythrocyte t½ using radiochromium as a tag was 2.4 days, and a reticulocyte survival study performed after labeling the cells with L-[14C]leucine indicated a t½ of 7.2 days. When stroma-free hemolysates were heated at 50°C, 16-20% of the hemoglobin precipitated. The thermolability was prevented by the addition of hemin, carbon monoxide, or dithionite, suggesting an abnormality of heme binding. An increased rate of methemoglobin formation was also observed after incubation of erythrocytes at 37°C. The abnormal hemoglobin could not be separated from hemoglobin A by electrophoresis or chromatography, but it was possible to isolate the variant β-chain by precipitation with p-hydroxymercuribenzoate. Purification of the β-chain by column chromatography followed by peptide mapping and amino acid analysis demonstrated a substitution of proline for β32 leucine. It appears likely that a major effect of this substitution is a disruption of the normal orientation of the adjacent leucine residue at β31 to impair heme stabilization.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 1746
page 1746
icon of scanned page 1747
page 1747
icon of scanned page 1748
page 1748
icon of scanned page 1749
page 1749
icon of scanned page 1750
page 1750
icon of scanned page 1751
page 1751
icon of scanned page 1752
page 1752
icon of scanned page 1753
page 1753
icon of scanned page 1754
page 1754
icon of scanned page 1755
page 1755
Version history
  • Version 1 (July 1, 1973): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts