thalassemia and Hb Lepore heterozygotes included in this study exhibit fetal hemoglobin levels varying from trace quantities to 14% (1.74 g/dl) of total hemoglobin in the adult. In this work, we have examined the correlation of DNA sequence polymorphisms with the observed HbF level. The analysis of polymorphic markers within the  globin cluster in 39 individuals heterozygous for  thalassemia or Hb Lepore confirms the previous findings for homozygous  thalassemia: the presence of both an (AT) 9 T 5 sequence configuration at position −540 of the  globin gene and a (C → T) variation at −158 of the G␥ globin gene is associated with elevated expression of HbF. However, at least one defective  globin gene is required to reveal this association. The best evidence is from the study of individuals heterozygous for Hb Lepore with various levels of HbF. In these individuals it was possible to explore the effect of a single (AT) x T y motif (the other being absent from the rearranged Lepore chromosome) on HbF expression. The presence of the (AT) 9 T 5 configuration increases HbF level from a median of 0.515 g/dl observed in (AT) 7 T 7 subjects, to 1.39 g/dl.We confirm the existence of linkage disequilibrium between the (C → T) variation at −158 of G␥ gene and the (TG) 13 configuration at the second intervening sequence (IVS-2) of A␥ gene and identify two new polymorphisms in this region: (TG) 7 (CG) 5 (TG) 8 linked to haplotype V and (TG) 8 (CG) 5 (TG) 10 linked to haplotype II. This study suggests that two distinct regions of the  cluster, whether in cis or in trans to each other, can interact to enhance HbF expression when a  thalassemic determinant is present in heterozigosity.
OBJECTIVE: To assess the prevalence of multiple sclerosis (MS) in the city of Santos, SP. METHOD: Evaluation of data from the Reference Center for MS of the coastal region of the State of São Paulo, from the Regional Association of Patients with MS (APEMBS), with active participation of all neurologists and neurosurgeons of the city, data from IBGE, from the city council, and from EMPLASA. The protocol proposed by the BCTRIMS (already used in other similar studies) was used for data collection and analysis, June 30th 2005 being established as the prevalence day. RESULTS: Santos has an area of 280.3 km², with 418,316 inhabitants (1.49 inhabitant per km²). A total of 65 patients were identified, attaining the prevalence of 15.54/100.000. The most frequent initial symptom of the disease was optical neuritis (28.8%). CONCLUSION: data from the city of Santos are similar to those already observed, but as yet not published, in other cities of the State of São Paulo and of Brazil.
We have estimated the incidence and molecular basis of alpha-thalassemia in a Portuguese population, mostly from the Greater Lisbon area. In a group of 100 consecutive cord blood samples, the gene frequency of the rightward deletion (-alpha 3.7) was 0.035, and the leftward deletion (-alpha 4.2) was 0.015. In this group, we have also found four heterozygotes for the triple alpha-globin gene rearrangement (alpha alpha alpha anti 3.7. gene frequency 0.020). We have characterized the subtypes of -alpha 3.7 and alpha alpha alpha anti 3.7 rearrangements. On the whole, these results give an incidence of 10% for deletional alpha-thalassemia carriers in the studied Portuguese population. In a group of 342 subjects presenting beta-thalassemia, or Hb S trait, beta-thalassemia major sickle cell disease or low red blood cell indices, the -alpha 3.7, -alpha 4.2, -SEA, -MED, (alpha alpha)MM, and alpha alpha alpha anti 3.7 haplotypes were found in different combinations. Only one nondeletional alpha-thalassemia determinant (a 5 nucleotide deletion in the alpha 2-globin gene in the second intervening sequence donor site) was detected, which might suggest a low incidence of these defects in the Portuguese population.
An autosomally transmitted hypochromic microcytic mild anaemia with elevated haemoglobin (Hb) A2 and globin chain imbalance has been observed in a three-generation family of Portuguese origin. Extensive DNA analysis of the beta-globin gene cluster, including the complete sequencing of the beta-globin gene and flanking regions, failed to reveal any genetic alteration. The co-segregation of sickle-cell trait in this family enabled us to postulate a defective erythroid trans-acting factor was playing a role in the down-regulation of both beta A- and beta S-globin genes. Among the transcription factors that could possibly have caused the reported phenotype, NF-E2 is unlikely to be implicated, whereas Nrf1 and Nrf2 cannot be ruled out. Thus, this family carries a novel beta-thalassaemia autosomal determinant unlinked to the beta-globin gene. This observation reinforces the notion of the haemoglobinopathies as single gene disorders under polygenic regulation.
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