Compound heterozygosity for two alpha-globin gene defects, Hb Taybe (alpha 1; 38 or 39 minus Thr) and a poly A mutation (alpha 2; AATAAA-->AATAAG), results in a severe hemolytic anemia.
We have identified two alpha-globin gene variations in an Arabian male with severe hemolytic disease through sequencing of amplified DNA of his alpha 2- and alpha 1-globin genes. One of the abnormalities involves a CAC (ACC or CCA) deletion between codons 36 and 41 of the alpha 1-globin gene. This leads to the synthesis of an abnormal alpha chain with one instead of two threonine residues at positions 38-39 and to the formation of the unstable Hb Taybe. The second variation is a mutation located in the poly A site of the alpha 2-globin gene (AATAAA-->AATAAG) which is common among Arabian people. Family studies have shown that the two variations are located on opposite chromosomes. The hemolytic disease in this man, resembling Hb H disease, is likely the result of a severe downregulation of both alpha-globin genes on the chromosome with the alpha 2 poly A mutation, and the instability of the alpha-Taybe chain being the product of an alpha 1-globin gene; this leaves only one alpha 2-globin gene normally active.
Pobedimskaya
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DD
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2100.
Molchanova
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TP
Streichman
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S
Huisman
T H
TH
D000328:Adult; D000595:Amino Acid Sequence; D000743:Anemia, Hemolytic / Q000209:etiology / Q000235:genetics*; D001483:Base Sequence; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis / Q000235:genetics; D015536:Down-Regulation; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA
D006455:Hemoglobins, Abnormal; D005914:Globins; D004247:DNA