Relative levels of alpha-, beta-, and gamma-mRNA from patients with severe and intermediate beta-thalassemia major.
We have determined the relative quantities of gamma- and beta-mRNAs and the alpha/beta-mRNA ratios in 37 patients with beta-thalassemia major with specific genotypes, namely 8 with a homozygosity for codon (CD) 39 (C-->T), 7 with a homozygosity for IVS-I-110 (G-->A), 5 with a homozygosity for IVS-I-6 (T-->C), for 15 patients with compound heterozygosities for 2 of these 3 mutations, and for 2 patients with the IVS-I-110 (G-->A)/-87 (C-->G) mutations. None had an alpha-thalassemia. Twelve patients had thalassemia intermedia and the remainder, transfusion-dependent severe conditions. Differences in phenotype were observed for compound heterozygotes involving the IVS-I-6 (T-->C) mutation in combination with either the IVS-I-110 (G-->A) or the CD 39 (C-->T) mutations: patients with thalassemia intermedia had a lower alpha/beta-mRNA ratio, about half of that of the patients with severe beta-thalassemia major. This might suggest a higher beta-mRNA synthesis in some patients than in others with the same genotype; mutations in promoter, enhancer, and/or locus control region sequences may be responsible for these differences. In vitro chain synthesis data were too incomplete to be helpful in this study. The RT-PCR procedure allowed the separation of abnormal (extended) mRNA from normal beta-RNA in subjects carrying the IVS-I-110 (G-->T) mutation. The relative quantities of this beta Th-mRNA (% of beta A + beta Th) were determined by scanning of the appropriate autoradiograms; they averaged 25% for homozygotes and about 4% for heterozygotes, indicating a considerable instability of the message.
Smetanina
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NS
Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta 30912-2114, USA.
Gu
L H
LH
Schilirò
G
G
Di Cataldo
A
A
Testa
R
R
Jakovlevska
Z
Z
Efremov
G D
GD
Huisman
T H
TH
D003062:Codon / Q000235:genetics; D005786:Gene Expression Regulation; D005838:Genotype; D005914:Globins / Q000145:classification / Q000235:genetics*; D006801:Humans; D017354:Point Mutation; D012333:RNA, Messenger / Q000097:blood*; D012720:Severity of Illness Index; D017086:beta-Thalassemia / Q000145:classification / Q000235:genetics*
D003062:Codon; D012333:RNA, Messenger; D005914:Globins