Delineation of specific β-thalassemia mutations in high-risk areas of Italy: A prerequisite for prenatal diagnosis

In this study, we defined by haplotype characterization combined with oligonucleotide hybridization or direct restriction endonuclease analysis the specific β-thalassemia mutations in a representative sample of β-thalassemia chromosomes from patients with homozygous β-thalassemia originating from different parts of Italy. We characterized the mutations in 90% of the thalassemia chromosomes and found that three mutations, namely the β⁺IVS 1-110, β°-39 and β⁺IVS 1-6 are prevalent in the Italian population. Most of the patients investigated were compound heterozygotes for two β-thalassemia mutations, and only a few were homozygotes for one mutant. One the basis of these findings, we predict that prenatal diagnosis in this population would be feasible in most cases by fetal DNA analysis with the oligonucleotide method using a limited number of oligonucleotide probes selected after screening parents for the most common β-thalassemia mutations. We have also devised a method based on hybridization with a mixture of two oligonucleotides that allows rapid and simultaneous screening of prospective parents for the two most frequent mutations in Italians, the β⁺IVS 1-110 and β°-39 mutants. This method may be applicable to prenatal diagnosis in cases at risk for the genetic compound of these mutations.