Advances in molecular diagnosis of inherited hemoglobin disorders

Molecular diagnosis for inherited disorders of hemoglobin production has been driven largely by the need for improved prenatal diagnosis. In turn, DNA-based testing has engendered better methods of fetal sampling. The sensitivity of DNA-based testing was increased tremendously by the polymerase chain reaction. Currently there are numerous polymerase chain reaction-based methods for diagnosing specific mutant globin alleles and detecting unknown mutations. These rely on restriction analysis, allele-specific hybridization or amplification, alterations in electrophoretic mobility, and DNA sequence analysis. The advantages and disadvantages of each are important to their specific application. The reverse dot blot method, with its capability for screening multiple alleles with a single hybridization reaction, is currently the most advantageous method for prenatal and routine clinical diagnosis.