A hemoglobin variant associated with neonatal cyanosis and anemia

Moira A. Crowley, Todd L. Mollan, Osheisa Y. Abdulmalik, Andrew D. Butler, Emily F. Goodwin, Arindam Sarkar, Catherine A. Stolle, Andrew J. Gow, John S. Olson, Mitchell J. Weiss

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Globin-gene mutations are a rare but important cause of cyanosis. We identified a missense mutation in the fetal Gγ-globin gene (HBG2) in a father and daughter with transient neonatal cyanosis and anemia. This new mutation modifies the ligandbinding pocket of fetal hemoglobin by means of two mechanisms. First, the relatively large side chain of methionine decreases both the affinity of oxygen for binding to the mutant hemoglobin subunit and the rate at which it does so. Second, the mutant methionine is converted to aspartic acid post-translationally, probably through oxidative mechanisms. The presence of this polar amino acid in the heme pocket is predicted to enhance hemoglobin denaturation, causing anemia.

Original languageEnglish
Pages (from-to)1837-1843
Number of pages7
JournalNew England Journal of Medicine
Volume364
Issue number19
DOIs
Publication statusPublished - 12 May 2011
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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