β^0-thalassemia having a 4-nucleotide deletion in codons 41 and 42 : first identification in Japanese

A β^0-thalassemia is defined as a heradetiarty, microcytis, hypochromic, hemolytic anemia due to no (β^0) or decreased (β^＋) production of the β-chain in cis to the defective β-globin gene. DNA sequencing of the cloned β-globin gene from a patient with β-thalassemia minor revealed for the first time in Japanese a delection of four nucleotides in coden 41-42 (TTCTTT → TT). Polymerase chain reaction and subsequent oligonucleotide hybridization analysis on other thalassemic patients detected the same defect in 5 of 28 unrelated families. This mutation causes frameshift at and 3' to codon 41 and generates an in-phase terminator at codon 59 of the β-globin gene. It constitutes a rather common subtype of β^0-thalassemia in some other Asian populations. The haplotypes and framewoks of the abnormal β-globin genes of the Japanese were common to those of Chinese and Southeast Asian rather than to those of Asian Indians. One of the nine heterozygous carries of the β^0-thalassemia had a clinical picture of thalassemia intermedia (rather than thalassemia minor). The resuts of restriction endonuclease mapping revealed that the patient was also hetrozygous for a tripicated α-globin gene. The presence of five (instead of four) functional α-globin genes in this patient appeared to responsible for the unusual clinical expression of the β^0-thalassemia.