Molecular basis of β-thalassemia in japan: Heterogeneity and origins of mutations

Chieko Wakamatsu, Motoshi Ichinose, Jun Ichi Manabe, Supan Fucharoen, Hiroyoshi Sawada, Shouichi Ohga, Junji Nishimura, Hideyuki Nukina, Takumi Harada, Satoshi Shirahata, Yuji Moriwaki, Naokuni Uike, Mitsuo Kozuru, Nagatomo Ohi, Mari Mineta, Michihisa Nomiyama, Yasuyuki Fukumaki

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Characterization of β-thalassemia mutations was attempted for 13 unrelated Japanese patients heterozygous for β-thalassemia. We have systematically analyzed β-thalassemia genes using polymerase-chain-reaction-related techniques; dot blot hybridization with oligonucleotide probes complementary to known mutations, restriction endonuclease assay and direct sequencing of amplified genomic DNA. Seven different mutations were detected. Six of them are an amber mutation in codon 90 (GAG to TAG), a four-base-pair deletion in codons 41 and 42 causing premature termination due to frameshift, a C-T substitution at position 654 of IVS-2, a G-A substitution at position 1 of IVS-2 and a C-G substitution at position 848 of IVS-2, leading to splicing defects, and an ocher mutation (GAA-TAA) in codon 121 causing a thalassemia intermedia phenotype with inclusion body formation in erythrocytes. A silent mutation (CTG-TTG) was also detected in codon 91 of the allele with the IVS-2 position 1 mutation. These mutations have been reported previously in the Japanese population. The other mutation is a novel one in the Japanese, an amber mutation (TGG-TAG) in codon 15, causing a β0-thalassemia phenotype by premature termination of the β-globin chain synthesis. We analyzed haplotypes of chromosomes bearing each β-thalassemia mutation. Origins and a spectrum of mutations in comparison with those detected in malaria-endemic regions are discussed.

Original languageEnglish
Pages (from-to)136-143
Number of pages8
JournalActa Haematologica
Issue number3
Publication statusPublished - 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology


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