Rapid molecular characterization of mutations leading to unstable hemoglobin β-chain variants

Abstract
Characterization of unstable hemoglobins by protein analysis is often difficult. However, it is facilitated by DNA analysis, especially in the case of hyperunstable β-chain variants, which produce a β-thalassemia phenotype. We have applied an efficient strategy to the detection of such variants at the DNA level, based on computer-designed denaturing gradient gel electrophoresis (DGGE) of amplified DNA fragments. This approach makes it possible to detect any anomaly in the β-globin gene. We describe the use of the DGGE method for rapid characterization of β-chain variants and report a new missense mutation in the β-globin gene third exon, β 127 CAG-CGG/Gln-Arg, which is responsible for the synthesis of a highly unstable hemoglobin.

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