A NEW MUTATION IN THE BETA-GLOBIN GENE (IVS II-850 G-C) FOUND IN A YUGOSLAVIAN BETA-THALASSEMIA HETEROZYGOTE

作者：JANKOVIC L; DIMOVSKI AJ; SUKAROVA E; JURICIC D; EFREMOV GD

来源：Haematologica-The Hematology Journal, 1992, 77(2): 119-121.

• BETA-GLOBIN GENE MUTATION
• BETA-THALASSEMIA
• POINT MUTATION
• SPLICING

Background. The recent development of laboratory techniques that can rapidly characterize the molecular defects of beta-thalassemia has resulted in the discovery of more than 100 different point mutations in the beta-globin gene. These mutations are population specific. About 20 of them account for over 90% of beta-thal genes in the world. The other mutations are usually found in single families. In this paper we describe a case with a novel mutation at position IVS II-850 (G-C) as a cause of beta-thalassemia.
Methods. Direct sequencing of PCR amplified DNA was used for the detection of the mutation. ASO probes were synthesized for dot-blot hybridization. Expression of the mutated allele was evaluated through Northern blot and RNA-PCR analyses.
Results. This mutation was found in four members of a family, who exhibited severe microcytosis and hypochromic anemia, with a average alpha/beta ratio of 2.0. The sequencing of PCR amplified DNA showed a G-C mutation at position IVS II-850 of the beta-globin gene. Dot blot analyses confirmed the presence of this substitution in all four carriers. Northern blot and RNA-PCR analyses did not reveal any abnormally spliced mRNA species.
Discussion. The G-C substitution at position IVS II-850 is the third mutation in the invariant AG dinucleotide of the acceptor splice site of the second intron of the beta-globin gene. It abolishes normal splicing, which leads to abnormally processed mRNA. It is a relatively rare mutation since it was not detected among the uncharacterized beta-thal chromosomes from Yugoslavia.

• 出版日期1992-4