β-Thalassemia in the Korean population
Thalassemia and Hemoglobinopathy
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 47 Korean families. Using direct sequencing of genomic DNA amplified through PCR and haplotype analysis, 44 β-thalassemia genes were characterized, all of which were heterozygous. Fourteen different mutations were identified. The common mutations noted included the intiation codon (CD) ATG->AGG (23.4%), CD 17 A->T (21.2%), and IVS-II-1 G->A (12.7%). Interestingly, mutations causing dominantly inherited β-thalassemia were common (17.0%). All cases of IVS-II-1 G->A mutations were linked to the silent mutation of CD 91 C->T of the-globin gene. The initiation CD ATG->AGG and IVS-II-1 G->A with CD 91 C->T were found in the Far East only, and may be inherited from a common origin for each mutation, at least in Koreans. CD17 A->T and CDs 41/42-TTCT were suggested to be introduced by gene-flow from southern China. Otherwise, Hb Korea, CDs 89/90-GT and a novel β-thalassemia mutation, CD 131 CAG->TAG, were only identified in Koreans. This mutation spectrum is characteristic of the low prevalent area of β-thalassemia, however it is quite different even from the adjacent countries, Japan or China.
KeywordsThalassemia Korean Population Common Mutation Globin Gene Silent Mutation
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Thein SL. Beta-thalassemia.Baillieres Clin Hematol
. 1998;11:91–126.CrossRefGoogle Scholar
Flint J, Harding RM, Boyce AJ, Clegg JB. The population genetics of the haemoglobinopathies.Baillieres Clin Hematol.
Huisman THJ, Carver MFH, Baysal E. A syllabus of thalassemia mutations, the sickle cell anemia foundation, augusta, GA, 1997 (http://globin.cse.psu.edu).Google Scholar
Park SS, Barnetson R, Kim SW, Weatherall DJ, Thein SL. A spontaneous deletion of beta 33/34 Val in exon 2 of the beta globin gene (Hb Korea) produces the phenotype of dominant beta thalassemia.Br J Haematol
. 1991;78:581–582.PubMedCrossRefGoogle Scholar
Koo MS, Kim SI, Cho HI, et al. A beta-thalassemia mutation found in Korea.Hemoglobin
. 1992;16:313–320.PubMedCrossRefGoogle Scholar
Ohba Y, Hattori Y, Harano T, et al. Beta-thalassemia mutations in Japanese and Koreans.Hemoglobin
. 1997;21:191–200.PubMedCrossRefGoogle Scholar
Kim J, Park SS, Yang SH, et al. A Korean family with a dominantly inherited β-thalassemia due to Hb Durham-N.C./Bresica [114(G16)Leu->Pro].Hemoglobin.
Chang JG, Lin CP, Liu TC, et al. Molecular basis of beta-thalassemia minor in Taiwan.Int J Hematol
. 1994;59:267–272.PubMedGoogle Scholar
Ko TM, Tseng LH, Hsu PM, Guu IJ, et al. Molecular characterization of beta-thalassemia in Taiwan and the identification of two new mutations.Hemoglobin
. 1997;21:131–142.PubMedCrossRefGoogle Scholar
Wakamatsu C, Ichinose M, Manabe J, et al. Molecular basis of beta-thalassemia in Japan: heterogeneity and origins of mutations.Acta Hematol
. 1994;91:136–143.CrossRefGoogle Scholar
Harano K, Harano T. Three kinds of initiation codon mutations of beta-thalassemia.Jpn J Clin Hematol
. 1990;31:1356.Google Scholar
Lam VM, Xie SS, Tam JW, Woo YK, Gu YL, Li AM. A new single nucleotide change at the initiation codon (ATG-> AGG) identified in amplified genomic DNA of a Chinese beta-thalassemic patient.Blood
Fucharoen S, Winichagoon P. Hemoglobinopathies in Southeast Asia: molecular biology and clinical medicine.Hemoglobin
. 1997;21:299–319.PubMedCrossRefGoogle Scholar
Flint J, Harding RM, Clegg JB, Boyce AJ. Why are some genetic diseases common? Distinguishing selection from other processes by molecular analysis of globin gene variauts.Hum Genet
. 1993;91:91–117.PubMedCrossRefGoogle Scholar
Harano T, Harano K, Ueda S. Application of polymerase chain reaction (PCR) to molecular analysis of the β-globin gene of the Japanese β0
-thalassemia-Hb San Diego [β109 (G11)Val-Met].Acta Hematol Jpn
. 1990;53:882–888.Google Scholar
Thein SL. Is it dominantly inherited beta thalassemia or just a beta-chain variant that is highly unstable?Br J Haematol
. 1999;107:12–21.PubMedCrossRefGoogle Scholar
Yamamoto K, Yamamoto K, Hattori Y, et al. Two beta-thalassemia mutations in Japan: codon 121 (GAA->TAA) and IVS-I-130 (G->C).Hemoglobin
. 1992;16:295–302.PubMedCrossRefGoogle Scholar
Hall GW, Barnetson RA, Thein SL. Beta thalassemia in the indigenous British population.Br J Hematol.
© The Japanese Society of Hematology 2002