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Abstract In this study we describe the Chinese IVS-II-654 (C-->T) betathalassemia mutation for the first time in an immigrant Turkish family living in Istanbul and originating from Xanthe, Greece. Four members of the family, representing 3 generations, are heterozygous for this mutation. A detailed family history demonstrated a Greek origin for members of 5 generations with no records of migration or consanguineous marriages. Analysis of polymorphic nucleotides located at the 5' end of the beta-globin chromosomes bearing the IVS-II-654 mutation in the family described carried the (AT)^sub 9^(T)^sub 5^ type of microsatellite sequence and the ACATCCCCA haplotype. These 2 haplotype components favor a non-- Eastern Asian origin for this chromosome, hence suggesting an independent origin for the IVS-II-654 mutation described in this family.
KEY WORDS: beta-THALASSEMIA, IVS-II-654, EAST ASIA, RARE MUTATIONS, ORIGIN OF MUTATION, TURKEY, GREECE
beta-Thalassemia is an autosomal recessive disorder characterized by microcytosis and hemolytic anemia and by diminished (beta^sup +^) or absent (beta^sup 0^) beta-globinchain synthesis (Huisman et al. 1997). Molecular analyses of betaglobin genes from Turkey revealed the presence of approximately 40 alleles causing the beta-thalassemia phenotype (Altay and Basak 1995; Tadmouri, Tozmen et al. 1998). This number is increasing as previously uncharacterized chromosomes are subjected to DNA sequencing (Tadmouri et al. 1997; Tadmouri, Saglamer et al. 1998; Tadmouri, Bilenoglu et al. 1998). In this communication we report the first observation of the Chinese IVS-II-654 (C->T) mutation (Cheng et al. 1984) in an immigrant Turkish family.
Subjects and Methods
Subjects. The proband was a 26-year-old pregnant woman who came in with her husband for prenatal diagnosis. The couple had been diagnosed as beta-thalassemia carriers in their hometown, Xanthe, Greece, from where they had migrated to Turkey 3 years ago. Once she was found to carry a rare mutation, members of her family, belonging to 3 generations, underwent hematological and molecular analyses. A detailed family history was also obtained.
DNA Isolation and Molecular Analysis. Blood samples were collected in tubes containing EDTA. Informed consent was obtained, and DNA was extracted from white blood cells according to the method of Poncz et al. (1982). In vitro amplification of genomic DNA was performed using the technique of Saiki et al. (1988). The mutations were investigated by reverse dotblot analysis (beta-Globin StripAssay Kit,...