title: 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 ligand-binding 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.
authors.affiliation: Division of Neonatology, Case Western Reserve University, Cleveland, USA.
authors.forename: Moira A
authors.initials: MA
authors.lastname: Crowley
authors.forename: Todd L
authors.initials: TL
authors.lastname: Mollan
authors.forename: Osheisa Y
authors.initials: OY
authors.lastname: Abdulmalik
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Butler
authors.forename: Emily F
authors.initials: EF
authors.lastname: Goodwin
authors.forename: Arindam
authors.initials: A
authors.lastname: Sarkar
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Stolle
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gow
authors.forename: John S
authors.initials: JS
authors.lastname: Olson
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Weiss
mesh_terms: D000740:Anemia / Q000235:genetics; D003490:Cyanosis / Q000235:genetics; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008706:Methemoglobin / Q000096:biosynthesis; D020125:Mutation, Missense; D010100:Oxygen / Q000097:blood; D011487:Protein Conformation; D017422:Sequence Analysis, DNA; D055545:gamma-Globins / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; D055545:gamma-Globins; D008706:Methemoglobin; D005319:Fetal Hemoglobin; D010100:Oxygen