Hb Lepore-Baltimore (δ^68Leu-β^84Thr) and Hb Lepore-Washington-Boston (δ^87Gln-β^IVS-II-8) in Central Portugal and Spanish Alta Extremadura

Abstract

Hb Lepore is one of the most common abnormal haemoglobins in Caucasians in Central Portugal and in the Spanish Alta Extremadura (0.28% in a survey of school children). A group of 19 Portuguese and 14 Spanish Hb Lepore carriers (all unrelated) was characterised at the molecular level by the polymerase chain reaction, sequencing and restriction enzyme analysis. The Portuguese and one Spanish carrier were heterozygous for Hb Lepore-Baltimore, whereas all other Spanish subjects were Hb Lepore-Washington-Boston carriers. Sequencing of the Hb Lepore-Baltimore gene further established the crossover at δ⁶⁸-β⁸⁴, a region two codons (CDs) shorter than that previously described and easily confirmed by digestion with MaeI and BanI. Data from haplotype analysis suggest that this crossover occurred as an independent event on the lberian Peninsula. The haematological data were similar in both groups except for the levels of Hb F and the ^Gγ chain, which were significantly higher in the Hb Lepore-Baltimore heterozygotes. Quantification of the globin chains and the mRNA transcripts showed that the δβ gene is transcribed at a higher level than the δ gene with levels of translation giving rise to 10%–15% of Hb Lepore. The different levels of Hb F observed in the two groups are the results of the higher transcription rate of the γ genes in Hb Lepore-Baltimore heterozygotes and an apparently less efficient translation of ^Gγ genes in Hb Lepore-Washington-Boston heterozygotes.