Role of apoptosis and its modulation in Alzheimer's disease: insights from in vitro and in vivo studies

Tese de doutoramento em Farmácia (Bioquímica), apresentada à Universidade de Lisboa através da Faculdade de Farmácia, 200

Deletional alpha-thalassemia and hematological phenotype: indicative parameters of the different deletions in the series from 2015 to 2019

As talassémias são caracterizadas por um desequilíbrio quantitativo nas cadeias globinicas devido à redução ou supressão da síntese de uma das cadeias. Foram avaliados retrospetivamente os resultados de 496 casos suspeitos de α-talassémia delecional e correlacionados com os dados hematológicos. A pesquisa de deleções causadoras de α-talassémia foi efetuada por Gap e Multiplex Gap-PCR. A maioria dos casos (n=190) apresentou um genótipo normal (αα /αα), seguido de heterozigotia (-α 3 ,7 /αα) (n=148) e homozigotia (-α 3 ,7 /α 3 ,7 ) (n=141) para a deleção de 3,7kb. Detetaram-se ainda 5 casos de heterozigotia para a deleção de 4,2Kb (-α 4,2 /αα), 4 de dupla heterozigotia ( α 3 ,7 /α 4,2 ), 7 de heterozigotia α 0 (-- S E A /αα ), e 1 de Hb H (-- S E A /-α 3 ,7 ). Os resultados evidenciaram que o VGM e o HGM são excelentes índices hematológicos de rastreio e seleção dos testes moleculares, sendo o seu valor tanto mais baixo quanto maior o número de genes delecionados. Os resultados obtidos são ainda concordantes com o descrito na literatura e reforçam que o valor de cut-off de 25 pg (HGM), tem sensibilidade adequada para inferir da presença de uma deleção α 0 -talassémia. A deteção da deleção α 0 assume particular importância na prevenção da ocorrência de Hb Bart’s na descendência de um casal de portadores. O diagnóstico de α-talassémia é efetuado por métodos moleculares, no entanto os índices hematológicos são importantes marcadores preditivos do número de genes alfa delecionados e da relação fenótipo / genótipo.Thalassemias are characterized by a quantitative imbalance of the globin chains due to the reduction or suppression of the synthesis of one of the globin chains. In the present study, we evaluated retrospectively 496 cases suspected of deletional α-thalassemia and we correlated them with the hematological data available. We searched for α-thalassemia deletions by performing Gap and Multiplex Gap-PCR. Most patients (n=190) had a normal genotype (αα /αα), followed by heterozygosity (-α 3 .7 /αα) (n=148) and homozygosity (-α 3 .7 /α 3 .7 ) (n=141) for the 3.7kb deletion. We also detected 5 cases of heterozygosity for the 4.2Kb deletion (-α 4 .2 /αα), 4 of double heterozygosity ( α 3 .7 /α 4 .2 ),7 heterozygosity α0 (-- SEA /αα ) and 1 of HbH (-- SEA /-α 3.7 ). The results showed that the MCV and the MCH are excellent hematological indices for screening and selection of patients for molecular testing (their value being the lower the greater the number of deleted genes ). Our results are in line with those described in the literature and reinforce that the cut-off value of 25 pg (HGM) is sensitive enough to infer the presence of an α0 -thalassemia deletion. The detection of the α0 deletion is very important in preventing the occurrence of Hb Bart's in the offspring of a carrier couple. Genetic testing makes the diagnosis of α-thalassemia, however hematological indices are relevant predictive markers of the number of deleted alpha genes and the phenotype /genotype correlation.info:eu-repo/semantics/publishedVersio

Deletional alpha-thalassemia and hematological phenotype: predictive parameters of different deletions

Introduction: Thalassemias are characterized by a quantitative imbalance of the globin chains due to the reduction or suppression of the synthesis of one of the globin chains.The hematological tests usually used as indicative for the investigation of α-thalassemia are the blood count with MCV (Mean Cell Volume) < 80 fL and/or MCH (Mean Cell Hemoglobin) < 27 pg and normal Hb A2 (< 3.5%). Aim: This study aimed to correlate the different deletional α-thalassemia genetic alterations with the corresponding hematological phenotype, based on casuistry from 2015 to 2019. Methodology: Was evaluated retrospectively 496 cases suspected of deletional α-thalassemia from 2015 to 2019 and correlated them with the hematological data available. We searched for α-thalassemia deletions by Gap-PCR and Multiplex Gap-PCR. Haematological evaluation was carried out by the erythrogram, Hb isoelectric focusing and quantification of Hb A2 and Hb F (Ion exchange high performance liquid chromatography). The statistical analysis of the results was carried out through calculating the mean, standard deviation, median, and t-Student test, with a significance level of 0.05. Results and discussion: Most patients (n=190) had a normal genotype (αα/αα), followed by heterozygosity (-α3.7/αα) (n=148) and homozygosity (-α3.7/α3.7) (n=141) for the 3.7kb deletion. We also detected 5 cases of heterozygosity for the 4.2Kb deletion (-α4.2/αα), 4 of double heterozygosity (α3.7/α4.2), 7 heterozygosity α0 (--SEA /αα) and 1 of HbH (--SEA/-α3.7). The results showed that the MCV and the MCH are excellent hematological indices for screening and selection of patients for molecular testing (their value being the lower the greater the number of deleted genes). Our results are in line with those described in the literature and reinforce that the cut-off value of 25 pg (MCH) is sensitive enough to infer the presence of α0 -thalassemia deletion. The detection of the α0 deletion is very important in preventing the occurrence of Hb Bart's in the offspring of a carrier couple. The diagnosis of deletional α-thalassemia is realised by genetic testing, however hematological indices are relevant predictive markers of the number of deleted alpha genes and the phenotype /genotype correlation.N/