Prenatal diagnosis of inherited hemoglobinopathies

This paper reviews the methodology available to make prenatal diagnosis of inherited hemoglobinopathies by DNA analysis and the strategy to be used for the large scale application of this procedure to high-risk populations. The most straightforward approach for prenatal diagnosis is nowadays based on the analysis of DNA enzymatically amplified by the polymerase chain reaction (PCR). The mutations, produced by gross structural rearrangement of the DNA and those affecting a restriction recognition site, are directly detected by visualization following ethidium bromide staining of the electrophoretic pattern resulting from enzymatic digestion of amplified DNA. The remaining ones are detected by dot blot analysis with allelic specific oligonucleotide probes. Because in each population a limited number of specific beta-thalassemia mutations are prevalent, prenatal diagnosis by DNA analysis may be carried out by a population-specific strategy based on the amplification of those regions of the beta-globin genes containing the mutations most frequently occurring in each population followed by dot blot analysis with allelic specific oligonucleotide probes. This approach has the great advantage of being very simple, because radioactive probes are not necessary, very rapid, the results being obtained within 24 hours from sampling and very sensitive, only a limited amount of DNA in the order of 50 ng being necessary.