β-THALASSEMIA IN THE KOREAN POPULATION

Abstract

β-Thalassemia is uncommon in the Korean population, however, it must be considered in the differential diagnosis of hypochromic anemia. The molecular characterization of β-thalassemia is absolutely necessary for molecular diagnosis as well as any genetic epidemiological study in this region. We analyzed the molecular basis of β-thalassemia in 38 Korean families. Using direct sequencing of genomic DNA amplified through polymerase chain reaction and haplotype analysis, 35 β-thalassemic genes were characterized, all of which were heterozygous. Twelve different mutations were identified. The most common mutations noted included the initiation codon ATG→AGG (β⁰) (28.9%), codon 17 (β⁰) (A→T) (18.4%), and IVS-II-1 (β⁰) (G→A) (10.5%). Interestingly, mutations causing dominantly inherited β-thalassemia were also common (15.7%). All four cases with the IVS-II-1 (G→A) mutation were linked to the silent mutation of codon 91 (C→T) of the β-globin gene. The initiation codon ATG→AGG and IVS-II-1 (G→A) with codon 91 (C→T) mutations were found in the Far East only, and may be inherited from a common origin for each mutation, at least in Koreans. The codon 17 (A→T) and codons 41/42 (β⁰) (−TTCT) were suggested to be introduced by gene-flow from southern China. Otherwise, only Hb Korea [codons 33/34 (β⁰) (−GTG)] and a novel β-thalassemic mutation, codons 89/90 (β⁰) (−GT), were identified in Koreans. This mutation spectrum is characteristic of the low prevalence area of β-thalassemia in Korea, it is, however, quite different from the adjacent countries, Japan and China.