β-Thalassemia Mutations in Japanese and Koreans

Ohba, Yusuke; Hattori, Yukio; Harano, Teruo; Harano, Keiko; Fukumaki, Yasuyuki; Ideguchi, Hiroshi

doi:10.3109/03630269708997524

Cited by 36 publications

(19 citation statements)

References 13 publications

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“…An unexplained high Hb A2 value of 6.1% was found for the 4 heterozygotes with the initiation CD (A->G) mutation. Recently, Ohba et al [19] reported data for heterozygotes with either one of 5 known ini tiation CD mutants, including 11 carriers with the ATG-+GTG change. These authors state that 'these mu tants seem to constitute a distinctive group among P°-thal mutations, giving the lowest average MCH and MCV, and the highest RBC and Hb A2 values.…”

Section: Discussionmentioning

confidence: 99%

Levels of Hb A<sub>2</sub> in Heterozygotes and Homozygotes for Beta-Thalassemia Mutations: Influence of Mutations in the CACCC and ATAAA Motifs of the Beta-Globin Gene Promoter

Huisman

1997

Acta Haematol

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The author summarizes the Hb A₂ levels in over 600 β-thalassemia heterozygotes with 32 different base changes or frameshifts and in 22 heterozygotes for 1 of 5 large deletions. Three major groups are recognized: persons with β°-thalassemia or β⁺-thalassemia (severe) have Hb A₂ levels between 4.5 and 5.5%, those with mild β⁺-thalassemia alleles have levels between 3.6 and 4.2%, with still lower values for those with silent mutations. High values were observed in subjects with the 2 mild β⁺ alleles with mutations in the β-globin gene promoter (-88, C→T and -29, A→G); unusually high Hb A₂ values were also present in several -88 and -29 homozygotes. Data for several members of 8 families in which the -88 (C→T) or the-29 (A→G) mutation, or the -1,393-bp deletion, is present in cis or in trans to a δ-globin gene mutation support earlier observations that an increase in δ-chain synthesis occurs in cis to either one of these 3 alleles. A review of these data confirms the suggestion that the increase in Hb A₂ levels results from at least two mechanisms: in a posttranslational system, the formation of αδ-dimers is promoted when excess α-chains are available, while certain promoter mutations increase the transcription of the δ-globin gene in cis because of a change in the binding of transcription factors.

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Section: Discussionmentioning

confidence: 99%

Levels of Hb A<sub>2</sub> in Heterozygotes and Homozygotes for Beta-Thalassemia Mutations: Influence of Mutations in the CACCC and ATAAA Motifs of the Beta-Globin Gene Promoter

Huisman

1997

Acta Haematol

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“…The GAA ! TAA termination codon at codon 121, which leads to the synthesis of a truncated b-globin chain, has been described in several families of different ethnic backgrounds (Stamatoyannopoulos et al 1974;Kazazian et al 1986;Fei et al 1989;Thein et al 1990;Ohba et al 1997), and in some families, heterozygotes do not have an unusually severe phenotype (i.e., the mutation is not dominantly inherited). Substantial amounts of mutant b-globin mRNA could be demonstrated in individuals in whom the mutation is dominantly inherited, but demonstration of the presence of the truncated b-globin variant has been difficult.…”

Section: Deletion or Insertion Of Intact Codonsmentioning

confidence: 99%

“…One mutation involves an insertion of 45 bp between positions -22 to þ23, thus affecting the initiation codon. The rest are single base substitutions, two affecting the first (A), three the second (T) and, three the third (G) nucleotide of ATG (Jankovic et al 1990;Lam et al 1990;Hattori et al 1991;Saba et al 1992;Ohba et al 1997;Forget 2001;Blacklock et al 2005;Thein and Wood 2009). It is theoretically possible for mutant b mRNAs to be initiated at the next downstream initiation codons, which are located at codons 21 and 22, or codon 55.…”

Section: Mutations Affecting the Initiation Codonmentioning

confidence: 99%

The Molecular Basis of -Thalassemia

Thein

2013

Cold Spring Harbor Perspectives in Medicine

293

189

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The b-thalassemias are characterized by a quantitative deficiency of b-globin chains underlaid by a striking heterogeneity of molecular defects. Although most of the molecular lesions involve the structural b gene directly, some down-regulate the gene through distal cis effects, and rare trans-acting mutations have also been identified. Most b-thalassemias are inherited in a Mendelian recessive fashion but there is a subgroup of b-thalassemia alleles that behave as dominant negatives. Unraveling the molecular basis of b-thalassemia has provided a paradigm for understanding of much of human genetics.

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“…The -thalassemia gene frequency in Koreans is roughly assumed to be about 0.1% or less as in Japanese (6). An analysis of -haplotypes is very useful for the genetic epidemiological study in this region, however, these characteristics have not been investigated in -thalassemia chromosomes of the Korean population.…”

Section: Introductionmentioning

confidence: 99%

RFLP Haplotypes of beta-Globin Gene Complex of beta-Thalassemic Chromosomes in Koreans

et al. 2002

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Korea is in the low-prevalence area of -thalassemia and the Korean population has relatively homogenous racial characteristics. Recently, we identified some causative mutations of the Korean -thalassemia patients. In order to elucidate the genetic background of -thalassemia alleles in Koreans, we determined the restriction fragment length polymorphism (RFLP)-haplotype and framework (FW) in nine -thalassemia chromosomes of five different causative mutations by PCR-based method and family linkage study. The result that the haplotype and the framework linked to the initiation codon ATG→AGG mutation were -+-++-+ and FW3A, respectively, in all of three families in this study suggests a common origin of this mutation at least in Koreans. A novel -thalassemia mutation, codons 89/90 -TG, showed discrepancy between -++-++-and FW1, which could be explained by gene conversion. A case of codons 8/9 +G frameshift mutation had +----++ and FW1. The linkage of the two -thalassemia mutations, codon 17 AAG→TAG and codons 41/42 -TTCT, with specific haplotypes and frameworks common to the Koreans and the neighboring countries suggests that those mutations are influenced by the genetic flow from the south China.

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β-Thalassemia Mutations in Japanese and Koreans

Cited by 36 publications

References 13 publications

Levels of Hb A<sub>2</sub> in Heterozygotes and Homozygotes for Beta-Thalassemia Mutations: Influence of Mutations in the CACCC and ATAAA Motifs of the Beta-Globin Gene Promoter

Levels of Hb A<sub>2</sub> in Heterozygotes and Homozygotes for Beta-Thalassemia Mutations: Influence of Mutations in the CACCC and ATAAA Motifs of the Beta-Globin Gene Promoter

The Molecular Basis of -Thalassemia

RFLP Haplotypes of beta-Globin Gene Complex of beta-Thalassemic Chromosomes in Koreans

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