β-Thalassehia Mutations in the Portuguese; High Frequencies of Two Alleles in Restricted Populations

Abstract

We report the characterization of seven different β-thalassemia mutations in 131 newly diagnosed Portuguese β-thalassemia heterozygotes. Methodology included the detection of abnormal fragments by agar gel electrophoresis of PCR-amplified DNA fragments after digestion with specific restriction endonucleases, as well as hybridization with synthetic nucleotide probes and sequencing of amplified DNA. Four mutations, including the newly discovered TGG→TGA change at codon 15, occurred in excess of 10% and accounted for some 90% of the β-thalassemia alleles in this population. The geographical distribution is uneven; the TGA→TGA mutation at codon 15 was primarily observed in the coastal region north of Lisbon, while the IVS-1-6 (T→C) mutation was confined to the central part of the country.