Delineation of specific beta-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 beta-thalassemia mutations in a representative sample of beta-thalassemia chromosomes from patients with homozygous beta-thalassemia originating from different parts of Italy. We characterized the mutations in 90% of the thalassemia chromosomes and found that three mutations, namely the beta+IVS 1–110, beta degrees -39 and beta+IVS 1–6 are prevalent in the Italian population. Most of the patients investigated were compound heterozygotes for two beta- thalassemia mutations, and only a few were homozygotes for one mutant. On 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 beta-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 beta+IVS 1–110 and beta degrees -39 mutants. This method may be applicable to prenatal diagnosis in cases at risk for the genetic compound of these mutations.