A hemoglobin variant associated with neonatal cyanosis and anemia

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 language	English
Pages (from-to)	1837-1843
Number of pages	7
Journal	New England Journal of Medicine
Volume	364
Issue number	19
DOIs	https://doi.org/10.1056/NEJMoa1013579
Publication status	Published - 12 May 2011
Externally published	Yes

ASJC Scopus subject areas

Medicine(all)

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10.1056/NEJMoa1013579

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Crowley, M. A., Mollan, T. L., Abdulmalik, O. Y., Butler, A. D., Goodwin, E. F., Sarkar, A., Stolle, C. A., Gow, A. J., Olson, J. S., & Weiss, M. J. (2011). A hemoglobin variant associated with neonatal cyanosis and anemia. New England Journal of Medicine, 364(19), 1837-1843. https://doi.org/10.1056/NEJMoa1013579

A hemoglobin variant associated with neonatal cyanosis and anemia. / Crowley, Moira A.; Mollan, Todd L.; Abdulmalik, Osheisa Y.; Butler, Andrew D.; Goodwin, Emily F.; Sarkar, Arindam; Stolle, Catherine A.; Gow, Andrew J.; Olson, John S.; Weiss, Mitchell J.

In: New England Journal of Medicine, Vol. 364, No. 19, 12.05.2011, p. 1837-1843.

Research output: Contribution to journal › Article

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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.",

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

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AU - Crowley, Moira A.

AU - Mollan, Todd L.

AU - Abdulmalik, Osheisa Y.

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AU - Goodwin, Emily F.

AU - Sarkar, Arindam

AU - Stolle, Catherine A.

AU - Gow, Andrew J.

AU - Olson, John S.

AU - Weiss, Mitchell J.

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AB - 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.

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