title: Comparative in vivo expression of beta(+)-thalassemia alleles.
abstract: Double heterozygotes who inherit one abnormal though stable beta-globin variant in association with a molecularly identified beta(+)-thalassaemia allele provide unique opportunities to quantify the in vivo expression of particular beta(+)-thalassemia alleles. The globin products of the two alleles can be separated, quantified and the output of the beta(+)-thalassaemia allele expressed as the MCH-beta(A) in pg beta(A)-globin/beta(+)-thalassemia allele/RBC = 0.5 MCH x Hb A%. In this communication we provide new quantitative data on the expression of five mutations as follows: the beta(+)-87 (C-->G) = 3.8 pg beta(A)-globin/beta(+)-thalassemia allele/RBC (n = 1); the beta(+) IVS-I-1 (G-->A) = 0.2 pg beta(A)-globin/beta(+)-thalassemia allele/RBC (n = 1); the beta(+) IVS-I-6 (T-->C) = 2.9 pg beta(A)-globin/beta(+)-thalassemia allele/RBC (n = 7); the beta(+) IVS-I-110 (G-->A) = 1.1 pg beta(A)-globin/beta(+)-thalassemia allele/RBC (n = 13), and the beta(+) IVS-II-745 (C-->G) = 1.74 pg beta(A)-globin/beta(+)-thalassemia allele/RBC (n = 2). The values obtained are compared with those of other beta(+)-thalassemia alleles from the literature. It can be seen that the MCH-beta(A) value may be a correct index of thalassemia severity useful for the correlation of genotype with phenotype, and for understanding the effects of mutations in beta-globin genes on pathophysiologically meaningful beta-globin gene expression.
authors.affiliation: Department of Pathology, University of Malta, Msida.
authors.forename: M M
authors.initials: MM
authors.lastname: Marwan
authors.forename: C A
authors.initials: CA
authors.lastname: Scerri
authors.forename: S O
authors.initials: SO
authors.lastname: Zarroag
authors.forename: A
authors.initials: A
authors.lastname: Cao
authors.forename: A
authors.initials: A
authors.lastname: Kyrri
authors.forename: E
authors.initials: E
authors.lastname: Kalogirou
authors.forename: M
authors.initials: M
authors.lastname: Kleanthous
authors.forename: P
authors.initials: P
authors.lastname: Ioannou
authors.forename: M
authors.initials: M
authors.lastname: Angastiniotis
authors.forename: A E
authors.initials: AE
authors.lastname: Felice
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005914:Globins / Q000032:analysis* / Q000235:genetics*; D006403:Hematologic Tests; D006454:Hemoglobins / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007558:Italy / Q000453:epidemiology; D008002:Libya / Q000453:epidemiology; D008297:Male; D008319:Malta / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D005914:Globins