Clinical, biochemical and molecular aspects of the talassemic syndromes in the population of Pernambuco State / Aspectos clinicos, bioquimicos e moleculares das sindromes talassemicas em população do estado de Pernambuco

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

? Thalassemia is a frequent inherited disease of the Hb molecule found in the majority of populations and distributed worldwide. The prevalence of this syndrome in Brazil has been studied for a long time, but due to limitations in the methodology of some research, data on prevalence and clinical diversity are not fully complete. Furthermore, as a consequence of our ethnic composition, mixed with an uneven distribuition of European, African, Asian and Indian native populations, the incidence of thalassemia may vary greatly from one region to another. This study aims to show clinical features, and also biochemical and molecular data of our thalassemia syndromes in a population setting of thalassemia patients in the State of Pernambuco. We studied 117 non-related patients, 11 of them with ? thalassemia major, 36 ? with thalassemia intermedia and 70 with the S/? thalassemia interaction, followed regularly at the Fundação HEMOPE ? Recife - Brazil. Molecular characterization was performed by PCR techniques and DNA sequencing. Characterization of ? thalassemia alleles showed 15 different mutations, 4 of which corresponded to 84.3% of the ? thalassemia alleles, in the following proportions: 54.9% IVS-I-6 (T-»C), 15.2% IVS-I-5 (G-»C), 7.9% codon 39 (C-»T) and 6.1% IVS-I-1 (G»A). Other rare mutations were found and for the first time in Brazil, such as: IVS-II-849 (A-»G), poly-A (T?C), -29 (A?G), codon 30 (A-»C), IVS-I-2 (T-»C), IVS-II-837 (T-»G), codons 106/107 (+G), as well as IVS-I-5 (G-»A) and -88 (C-»T) mutations. A new mutation is also described: codon 12 (-C). We found 30 homozygous patients for the IVS-I-6 (T-»C) mutation, which showed a strong association with the ? gene haplotype VI. The IVS-I-5 (G-»C) mutation was related to the ? gene haplotype I, differently from that found in other populations studied (? haplotype VII) where it is more prevalent, suggesting a different origin for this mutation in Brazil. The -?3.7 kb deletion was present in 4.2% of ? thalassemia homozygous patients and in 15.7% of the S/? thalassemia patients, whereas the ???anti3.7kb was found in 5.7% of them. The XmnI polymorphism was present in 6.1% of the homozygous ? thalassemia patients and in only 1.4% of the S/? thalassemia individuals. In relation to the UGT1A1 allele, we found that patients with genotypes (TA) 7 / (TA) 7 and (TA) 7 / (TA) 8 showed higher levels of non-conjugated bilirrubin and seem to be more prone to developing gall stones. In Brazil, although the ethnic composition is markedly heterogeneous, the most common mutations are of Mediterranean origin; Pernambuco may be a curious exception to this, since around 16.0% of the thalassemia population have mutations of Asian origin and 10.8% of African origin. In conclusion, the diversity of the mutations found and their frequencies greatly differ from those found in other Brazilian populations studied previously, for example in the Southeast where only four thalassemia mutations are responsible for the majority (97%) of the thalassemia cases, although the commonest mutation is the ?039 (C-»T)

ASSUNTO(S)

talassemia beta beta thalassemia phenotype genotipo fenotipo genotype

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