Screening and prenatal diagnosis of the haemoglobinopathies

In this paper we have reviewed the social and technical aspects of carrier screening and prenatal diagnosis of the inherited haemoglobinopathies. The characteristics of programmes based on carrier screening and prenatal diagnosis ongoing in a number of at-risk Mediterranean populations have been described. The most relevant and common aspects of these programmes are the continuous educational campaign directed to the population at large, the voluntary basis and non-directive counselling. The target population has been most commonly couples before or after marriage. The vast majority of couples counselled accepted prenatal diagnosis. All programmes have encountered a high degree of success as indicated by the marked reduction in the birth rate of infants with thalassaemia major. No significant adverse effects have been reported. A programme with similar characteristics and for which the preliminary results are encouraging, is operating for sickle cell anaemia in the Cuban population. In a population with high frequency of hydrops fetalis, screening for deletion alpha-thalassaemia is recommended to prevent the negative effects on a pregnant woman of the presence of an hydropic fetus. Thalassaemia carrier screening is now carried out by automatic red cell indices and HbA2 determination. Definition of atypical cases may require iron studies, globin chain synthesis determination and/or alpha, beta- and delta-globin gene analysis. Identification of the carrier state is followed by definition of the mutation on enzymatically amplified DNA. Known mutations may be detected by restriction endonuclease analysis, non-denaturing polyacrylamide gel electrophoresis, allele-specific primers or allele-specific probes. The most promising procedures, which are also amenable to complete automation are reverse oligonucleotide hybridization and primer-specific amplification. Unknown mutations are defined by denaturing gradient gel electrophoresis, single-strand conformation polymorphism analysis, and chemical mismatch cleavage analysis followed by direct sequencing. The same methods on enzymatically amplified chorionic villus DNA are used for prenatal diagnosis. The potential pitfall resulting from maternal contamination can be avoided by careful dissection of the maternal decidua from the chorion and by the simultaneous amplification of a suitable polymorphism.