title: Molecular basis of beta-thalassemia in Japan: heterogeneity and origins of mutations.
abstract: Characterization of beta-thalassemia mutations was attempted for 13 unrelated Japanese patients heterozygous for beta-thalassemia. We have systematically analyzed beta-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 beta zero-thalassemia phenotype by premature termination of the beta-globin chain synthesis. We analyzed haplotypes of chromosomes bearing each beta-thalassemia mutation. Origins and a spectrum of mutations in comparison with those detected in malaria-endemic regions are discussed.
authors.affiliation: Institute of Genetic Information, Kyushu University, Fukuoka, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Wakamatsu
authors.forename: M
authors.initials: M
authors.lastname: Ichinose
authors.forename: J
authors.initials: J
authors.lastname: Manabe
authors.forename: S
authors.initials: S
authors.lastname: Fucharoen
authors.forename: H
authors.initials: H
authors.lastname: Sawada
authors.forename: S
authors.initials: S
authors.lastname: Ohga
authors.forename: J
authors.initials: J
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Nukina
authors.forename: T
authors.initials: T
authors.lastname: Harada
authors.forename: S
authors.initials: S
authors.lastname: Shirahata
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003062:Codon; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015151:Immunoblotting / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D015183:Restriction Mapping; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D003062:Codon