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 | |
| Publication status | Published - 12 May 2011 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Medicine(all)
Cite this
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
}
TY - JOUR
T1 - A hemoglobin variant associated with neonatal cyanosis and anemia
AU - Crowley, Moira A.
AU - Mollan, Todd L.
AU - Abdulmalik, Osheisa Y.
AU - Butler, Andrew D.
AU - Goodwin, Emily F.
AU - Sarkar, Arindam
AU - Stolle, Catherine A.
AU - Gow, Andrew J.
AU - Olson, John S.
AU - Weiss, Mitchell J.
PY - 2011/5/12
Y1 - 2011/5/12
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=79955887767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955887767&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1013579
DO - 10.1056/NEJMoa1013579
M3 - Article
C2 - 21561349
AN - SCOPUS:79955887767
VL - 364
SP - 1837
EP - 1843
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 19
ER -