We have delineated the molecular lesions causing β-thalassemia in Spain, a country that has witnessed the passage of different Mediterranean populations over the centuries, in order to evaluate the extent of heterogeneity of these mutations and to make possible simplified prenatal diagnosis of the disorder in that country. The use of the polymerase chain-reaction (PCR) technique to preferentially amplify β-globin DNA sequences that contain the most frequent β-thalassemia mutations in Mediterraneans enabled us to rapidly analyze 58 β-thalassemia alleles in a dot-blot format either by hybridization with allele-specific radiolabeled oligonucleotide probes or by direct sequence analysis of the amplification product. The Spanish population carries seven different β-thalassemia mutations; the nonsense codon 39 is predominant (64%), whereas the IVS1 position 110 mutation, the most common cause of β-thalassemia in the eastern part of the Mediterranean basin, is underrepresented (8.5%). The IVS1 mutation at position 6 accounts for 15% of the defects and leads to a more severe form of β+-thalassemia than originally described in most of the patients we studied. In this study, we demonstrate further the usefulness of the dot-blot hybridization of PCR-amplified genomic DNA in both rapid population surveys and prenatal diagnosis of β-thalassemia.
|Number of pages||6|
|Journal||American Journal of Human Genetics|
|Publication status||Published - 1988|
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