Identification of hemoglobin G-Philadelphia (alpha 68 Asn replaced by Lys) and hemoglobin Matsue-Oki (alpha 75 Asp replaced by Asn) in a black infant.
Two alpha-chain variants, Hb G-Philadelphia and Hb Matsue-Oki, were present in members of a relatively large black family from South Carolina. The four Hb G-Philadelphia heterozygotes averaged 35.6% Hb G, suggesting the presence of an alpha-thalassemia-2 condition in cis to the Hb G mutation, which was confirmed by DNA structural analysis. The seven Hb Matsue-Oki heterozygotes averaged 22.2% Hb MO and likely have four active alpha-chain genes. One infant was a compound heterozygote for the two Hb variants which could not be separated from each other. The quantity of Hb G plus Hb MO was 58% by DEAE-cellulose chromatography and 69% by chain analyses. These results and the family data indicate that this child had three active alpha-chain genes, of which one regulated the synthesis of the normal alpha chain, one was mutated to give the alpha G chain, and one to give the alpha MO chain. The amino acid substitutions in Hb G-Philadelphia and Hb Matsue-Oki are located in the tryptic peptide alpha T-9, which is 29 amino acid residues long. Structural analyses of these abnormalities made use of high-pressure liquid chromatography for the separation of both tryptic and thermolytic peptides and of a highly sensitive ultra-micro sequencing procedure. Although the alpha 68 Asn replaced by Lys substitution is readily demonstrable in Hb G-Philadelphia the elucidation of the alpha 75 Asp replaced by Asn replacement in Hb Matsue-Oki was greatly facilitated by the use of these microprocedures.
D000293:Adolescent; D000328:Adult; D001216:Asparagine; D001224:Aspartic Acid; D044383:Black People; D002648:Child; D005260:Female; D006580:Genetic Carrier Screening; D014644:Genetic Variation; D006455:Hemoglobins, Abnormal / Q000302:isolation & purification*; D006801:Humans; D007223:Infant; D008239:Lysine; D008297:Male; D009154:Mutation; D010375:Pedigree; D010446:Peptide Fragments / Q000032:analysis; D013789:Thalassemia / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D010446:Peptide Fragments; D001224:Aspartic Acid; C036347:hemoglobin Matsue-Oki; D001216:Asparagine; C031679:hemoglobin G Philadelphia; D008239:Lysine