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Compound heterozygosity for two beta chain variants: the mildly unstable Hb Tyne (codon 5 Pro›Ser) and HbS (codon 6 Glu›Val)
Compound heterozygosity for Hb Tyne and HbS, that is very rare, was identified by direct DNA sequencing of the beta-globin gene in a Turkish patient. Hematological investigation of a girl at the age of 9 due to the presence of HbS (40.7%) led to the identification of a compound heterozygosity at codons 5-6. This was found to be the result of substitution of cytosine (C) for thymidine (T) at the fifth position and a substitution of adenine (A) for thymidine (T) at the sixth position of the beta globin gene. As a result of these mutations, the order of amino acids at codons 5-6 was changed from Pro-Glu to Ser-Val, respectively. Since the co-inheritance of Hb Tyne and HbS had not been reported in literature before, our case set an example for identification of coinheritance of Hb Tyne and HbS for the first time. Therefore, such cases may be considered as an important example for understanding the structural variants of hemoglobin and may provide important clues for critical amino acids responsible for stabilization of hemoglobin tetrameric structure and genetic counseling.

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Authors: Özlem Güzeloğlu Kayışlı, İbrahim Keser, Osman Nidai Özeş, Duran Canatan, Akif Yeşilipek, Güven Lüleci

Keywords: Hemoglobin S, Hemoglobin Tyne, Beta-globin, Heterozigosite, DNA dizi analizi.

  • Year: 2005
  • Number: 1
  • Referance No: 58336

  • Figure 1. Direct DNA sequence analysis of the mutated strand of a beta-globin gene PCR fragment from the compound heterozygous for Hb Tyne and HbS proband. The normal sequence is shown on the left, and the mutated sequence on the right. The base where substitution of cytosine (C) for tymidine (T) in codon 5 are indicted by a asterisk (*).

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