HH LEPORE-BALTIMORE (DELTA(68LEU)-BETA(84THR)) AND HH LEPORE-WASHINGTON-BOSTON (DELTA(87GLN)-DELTA(IVS-II-8)) IN CENTRAL PORTUGAL AND SPANISH ALTA-EXTREMADURA

Hb Lepore is one of the most common abnormal haemoglobins in Caucasian s 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 le vel by the polymerase chain reaction, sequencing and restriction enzym e analysis. The Portuguese and one Spanish carrier were heterozygous f or Hb Lepore-Baltimore, whereas all other Spanish subjects were Hb Lep ore-Washington-Boston carriers. Sequencing of the Hb Lepore-Baltimore gene further established the cross-over at delta(68)-beta(84), a regio n two codons (CDs) shorter than that previously described and easily c onfirmed by digestion with MaeI and BanI. Data from haplotype analysis suggest that this crossover occurred as an independent event on the I berian Peninsula. The haematological data were similar in both groups except for the levels of Hb F and the (G) gamma chain, which were sign ificantly higher in the Hb Lepore-Baltimore heterozygotes. Quantificat ion of the globin chains and the mRNA transcripts showed that the delt a beta gene is transcribed at a higher level than the delta gene with levels of translation giving rise to 10%-15% of Hb Lepore. The differe nt levels of Hb F observed in the two groups are the results of the hi gher transcription rate of the gamma genes in Hb Lepore-Baltimore hete rozygotes and an apparently less efficient translation of (G) gamma ge nes in Hb Lepore-Washington-Boston heterozygotes.