Hemoglobin Denver [alpha 2 beta 2(41) (C7) Phe-->Ser]: a low-O2-affinity variant associated with chronic cyanosis and anemia.
OBJECTIVE
To report a previously undescribed low-O2-affinity hemoglobin variant that is associated with chronic cyanosis.


METHODS
Pertinent laboratory and historical data for the index case (from Denver, Colorado) and certain family members were recorded, and the hemoglobin variant was characterized.


METHODS
Electrophoresis, high-performance liquid chromatography (HPLC), and isoelectric focusing were used to examine blood specimens for the presence of hemoglobin variants, and the O2 affinity of whole blood was determined. The abnormal peptide detected on reverse-phase HPLC of separated globin chains was analyzed for its amino acid composition and sequence.


RESULTS
Although no abnormal hemoglobin band separated from hemoglobin A on electrophoresis, HPLC, and isoelectric focusing, a heat test showed hemoglobin instability, and O2 affinity studies disclosed an appreciably right-shifted dissociation curve. On chromatography, the new variant--hemoglobin Denver--was found to be due to a substitution of serine for phenylalanine at position 41 (C7) in the beta chain. In addition to substantial reduction in O2 affinity, hemoglobin Denver is accompanied by moderate reticulocytosis and mild anemia.


CONCLUSIONS
Hemoglobin Denver causes no clinical symptoms other than cyanosis, which is attributable to the low O2 affinity.
Stabler
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Department of Medicine, University of Colorado School of Medicine, Denver.
Jones
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Head
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Shih
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Fairbanks
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D000293:Adolescent; D000595:Amino Acid Sequence; D000740:Anemia / Q000097:blood* / Q000150:complications / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D003490:Cyanosis / Q000097:blood* / Q000150:complications / Q000235:genetics; D004586:Electrophoresis; D030342:Genetic Diseases, Inborn / Q000097:blood* / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011487:Protein Conformation; D017701:Reticulocyte Count
D006455:Hemoglobins, Abnormal; C086293:hemoglobin Denver