
The present study provides information about the alpha / beta and alpha 2 / alpha 1-mRNA ratios in reticulocytes of normal adults and individuals with different alpha-globin gene deficiencies; it found its origin in analytical data of blood samples from a Laotian couple and their newborn baby. The father carried the 4.2 kb deletion on one chromosome and a TAA --> CAA mutation at the terminating codon of the alpha 2 gene (Hb Constant Spring or CS) on the other chromosome. The mother had the 3.7 kb deletion on one chromosome and a TA A --> TAT mutation at the terminating codon of the alpha 2-globin gene (Hb Paksé) of the second chromosome. The baby was a compound heterozygote for the two termination codon mutations. The mRNA data for this family were compared to those for persons with several well-defined alpha-globin gene deficiencies. The results confirm the importance of the alpha 2 alpha 1-mRNA for the synthesis of alpha chains in alpha-thalassemia-2 homozygotes (-alpha/-alpha) and in patients with Hb H disease due to the deletion of three alpha-globin genes (-alpha/--). Furthermore, the MRNA production of the alpha 1-globin gene on the chromosome with the alpha CS mutation (alpha CS alpha) is only one-half of that by the alpha 2 alpha 1-globin gene of a chromosome with a 3.7 or 4.2 kb deletion, explaining the greater severity of, and higher Hb H level in Hb H patients with the alpha CS alpha condition (alpha CS alpha/--) as compared to those with the three gene deletion (-alpha/--). The methodology could be useful as a preliminary screening for the presence of point mutations leading to the functional loss of a single alpha-globin gene, provided common deletional alleles have been excluded.
Adult, Male, Hemoglobin H, Reticulocytes, Base Sequence, Genotype, Hemoglobins, Abnormal, Molecular Sequence Data, Infant, Newborn, Polymerase Chain Reaction, Globins, Gene Expression Regulation, alpha-Thalassemia, Humans, Point Mutation, Female, RNA, Messenger, Codon, Sequence Deletion
Adult, Male, Hemoglobin H, Reticulocytes, Base Sequence, Genotype, Hemoglobins, Abnormal, Molecular Sequence Data, Infant, Newborn, Polymerase Chain Reaction, Globins, Gene Expression Regulation, alpha-Thalassemia, Humans, Point Mutation, Female, RNA, Messenger, Codon, Sequence Deletion
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