Browsing by Author "Estevinho, A."
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- Advances in the genotyping of thrombosis genetic risk factors: clinical and laboratory implications.Publication . Cabeda, J.; Pereira, M.; Oliveira, J.; Estevinho, A.; Pereira, I.; Morais, S.; Justiça, B.; Campos, M.Since FV-Leiden polymorphism was first described in 1994, a growing number of polymorphic loci have been identified in association with increased genetic risk for thrombophilia. Often however, these risk factors have been studied in isolation of the remaining known phenotype linked polymorphisms. This fact has, at least in part, been justified by the laborious techniques traditionally used in the genotyping studies, as well as its relatively high costs. Another major problem concerning these studies has been the non-negligible incidence of dubious genotypes, resulting from the manual, labour intensive techniques applied, and their sometimes difficult to read output's. These difficulties have also hampered the widespread use of genotyping data in the clinical assessment of the genetic risk levels both in patients and their relatives, leaving some clinicians less than convinced about its clinical usefulness. Recently however, the introduction of new genetic techniques in the clinical genetics laboratory has started to change this picture. Most notably, the advent of Real-time-PCR has brought the possibility of genotyping patients and controls at a large scale, with increased specificity, automation and speed. Moreover, the use of these techniques in the clinical genetics setting has not only increased the quality of the results, but most importantly has also increased our capability of answering questions at a deeper level. Among the new questions that can now be answered without increased costs and uncertainty is the study of the association of genetic risk factors in thrombophilia. Our results show that indeed even common polymorphic loci may increase our ability to further discriminate the genetic thrombosis risk of individual patients and relatives. It must however be noted that the innovation level in the clinical genetics lab is just starting to grow. In fact we haven't even started to experience the advantages brought about by the genome program, and its massive identification of SNP's. The technology to test these is also presently being refined, and is expected to go from research to the clinical lab in the near future. Only then, can we expect to define with high certainty the combined genetic risks for such complex pathologies as the thrombophilias.
- Unexpected pattern of beta-globin mutations in beta-thalassaemia patients from northern PortugalPublication . Cabeda, J.; Correia, C.; Estevinho, A.; Simões, C.; Amorim, M.; Pinho, L.; Justiça, B.We characterized the genetic nature of beta-thalassaemia in northern Portugal. Of the 164 patients studied three were beta-thalassaemia major cases (one IVS-1-6/beta degrees 39 and two homozygous IVS-1-110). The analysis of the frequency of each mutation in the families revealed that the codon 6(-A) mutation was unexpectedly frequent (40%) and associated with the beta-globin haplotype E, and not with the usual European and North African CD6(-A) haplotypes. In contrast, the frequency of IVS-1-6 (8%) and beta degrees 39 (19%) was found to be lower than in the rest of the country. The frequency of all other mutations was similar to previous reports for central/southern Portugal. Six families carried none of the most frequent mutations in the Mediterranean area. These families were studied by gene sequencing, revealing that three families carried a previously described mutation (CD16 G --> A). The remaining families carried previously unidentified mutations: one showed an 86 bp insertion in exon 2 (named HGSA) and two showed a deletion of a cytidine in codon 11 (CD11(-C)). The results, showing a high frequency (82%) of beta degrees mutations, strongly indicates that genetic counselling should be intensified as a means of preventing the spread of the severe mutations found.