Browsing by Issue Date, starting with "2019-03-15"
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- SCARB2 mutations as modifiers in Gaucher disease: the wrong enzyme at the wrong place?Publication . Coutinho, Maria Francisca; Lacerda, L.; Gaspar, A.; Pinto, E.; Ribeiro, I.; Laranjeira, F.; Ribeiro, H.; Silva, E.; Ferreira, C.; Prata, M.J.; Alves, S.Unlike most lysosomal proteins, β-glucocerebrosidase (GCase), the hydrolase defective in Gaucher disease (GD), is delivered to lysosomes through its interaction with the transmembrane protein LIMP2. A few years ago, mutations in its coding gene, SCARB2, were reported to modify the severity of GD phenotype. The existence of a great variety of GD phenotypes is well-known, with numerous patients who carry identical genotypes presenting remarkable phenotypic variability. Over the years, that variability has been attributed to other genetic, epigenetic and/or environmental factors. Still, there is still much to learn on this subject. Recently, an association between Parkinson's disease (PD) and the presence of mutations in the GBA gene has been demonstrated. Moreover, there are also studies suggesting that genetic variants in the SCARB2 gene may also be risk factors for PD. We analysed the SCARB2 gene in the Portuguese cohort of 91 GD patients, having identified 3 different SCARB2 coding variants. Of those, 2 were known polymorphisms with high prevalence in the normal population (p.M159V and p.V396I) and the third was a novel coding variant, p.T398M, present in heterozigousity in a single patient. Our study demonstrated that, at least for the Portuguese population, genetic variability at SCARB2 does not account much to the GD phenotypic spectrum. Nevertheless, in vitro analyses of the novel p.T398M are envisaged, in order to further characterize the effect of this variant on the levels and sub-cellular location of GCase. The clinical presentation of the patient harbouring this coding variant will also be discussed.
- Patologia benigna da tiróide e cancro da mamaPublication . Duarte, Daniela; Rodrigues, Ana PaulaObjetivos primários: Estimar a prevalência de patologia benigna da tiroide em mulheres adultas e com antecedentes de Ca mama; Estimar a prevalência de patologia benigna da tiroide em mulheres adultas sob observação na Rede MS. Objetivo secundário: Comparar a prevalência de patologia benigna da tiroide nas mulheres com antecedentes de Ca mama com a prevalência de patologia benigna da tiroide estimada na população feminina da Rede MS.
- Fatores de risco e eventos cardiovasculares na população da Rede Médicos-SentinelaPublication . Gaio, Vânia; Sousa Uva, Mafalda; Matias Dias, Carlos; Rodrigues, Ana PaulaAs doenças do aparelho circulatório são a principal causa de morte em Portugal. Em 2016, a doença isquémica cardíaca e o acidente vascular cerebral (AVC) foram as duas principais causas de mortalidade prematura da população portuguesa. O Enfarte Agudo do Miocárdio (EAM) e o AVC, bem como alguns fatores de risco destes dois eventos cardiovasculares, nomeadamente a hipertensão arterial (HTA), a diabetes mellitus (DM) e a dislipidémia foram alvo de notificação na Rede Médicos-Sentinela durante vários anos desde 1989. O presente trabalho tem como objetivo descrever a evolução das taxas de incidência anuais de EAM, AVC, HTA, DM e dislipidémia na população portuguesa com 15 ou mais anos de idade, entre 1990 e 2017. Foi calculada a taxa de incidência anual padronizada para a idade (população padrão europeia) de AVC, EAM, HTA, DM e dislipidémia na população com 15 ou mais anos de idade nos anos em que estes eventos estiveram em notificação na Rede Médicos Sentinela, entre 1990 e 2017. As taxas de incidência anuais foram estratificadas por sexo. Os novos casos desses eventos foram notificados a partir da lista de utentes de cada Médico-Sentinela, de acordo com o melhor conhecimento clínico da situação. Em 2017 a taxa de incidência padronizada de EAM (83,8/105) atingiu o valor mais baixo desde 1994. Observou-se uma acentuada redução da incidência de HTA em 2017 (765,1/105 no sexo masculino e 669,7/105 no sexo feminino), contrariando a tendência crescente dos últimos anos. No entanto, no que se refere à taxa de incidência de AVC registou-se um decréscimo até 2016, seguido de um aumento em 2017 em ambos os sexos (302,3/105 no sexo masculino e 122,8/105 no sexo feminino). As taxas de incidência de HTA, DM, AVC e EAM foram mais elevadas no sexo masculino, ao longo do período em estudo, indicando um maior risco neste sexo. Estes resultados encontram-se de acordo com os dados de mortalidade cardiovascular para a população portuguesa. As quebras nestas séries temporais são limitadoras da interpretação das variações das taxas de incidência, demonstrando a necessidade de manter a notificação permanente destes problemas de saúde de forma a ser possível estimar a sua tendência, acrescida ao facto da Rede Médicos-Sentinela ser a única fonte que disponibiliza dados epidemiológicos desta natureza para a população portuguesa.
- Estudo de dislipidemias familiares de causa monogénica rara e poligénicaPublication . Alves, Ana CatarinaDyslipidaemia is one major risk factors for cardiovascular disease (CVD), which is the leading cause of death in Portugal and worldwide. The identification the origin of the dyslipidaemia improves patient outcomes since, depending on the affected pathway, a more personalized treatment can be offered to avoid the consequences of the lipid metabolism disruption. The molecular diagnosis of the different types of dyslipidaemia allows the correct diagnosis in which treatment can be based. There are two major groups within the vast theme of dyslipidaemia: hypercholesterolaemias and hypertriglyceridaemias. Familial hypercholesterolaemia (FH), an autosomal dominant disorder, is the most common monogenic disorder associated with an increased cardiovascular risk with a prevalence of 1/250-1/500. For this reason, the identification of patients with FH should be a health priority. Three genes have been associated to FH: LDLR, APOB, PCSK9. Familial hypertriglyceridaemias also confers a high cardiovascular risk as in Familial Combined Hyperlipidaemia (FCHL), a polygenic disorder, or can lead to other complications, as pancreatitis, in Familial Lipoprotein Lipase Deficiency (FLLD), an autosomal recessive disorder due to mutations in LPL or its co-factor APOC2. There are also other rare recessive dyslipidaemia associated with low levels (below the 5th percentile for age and sex) of one or more lipid particles namely LDL, HDL and triglycerides. Dyslipidaemia presenting low LDL levels can be due to stop mutations in APOB (hypobetalipoproteinaemia, FHBL) or mutations in MTTP gene (abetalipoproteinaemia, ABL), two autosomal recessive disorders. Patients these two disorders may manifest a variety of symptoms and signs affecting several organs (steatorrhea, neurological and ophthalmological symptoms, non-alcoholic fatty liver disease). Another group of dyslipidaemia are the ones that cause low HDL values (below the 5th percentile for age and sex) and usually presents with increase cardiovascular risk. The best know is Tangier disease, an autosomal recessive disorder caused by mutations in ABCA1 gene and HDL deficiency, an autosomal dominant disorder caused by mutations in ABCA1 and APOA1 genes. At the National Institute of Health dyslipidaemia diagnosis is performed at present time by Next Generation Sequencing with 4 different panels: the FH panel (LDLR, APOB, PCSK9, LDLRAP1, LIPA, APOE and ABCG5/8 genes); Familial Hypertriglyceridaemia panel (LPL, APOC2, APOA5, APOC3, LMF1, GPD1, LIPA, GPIHBP1 and APOE genes); Disorders associated with HDL panel (APOA1, ABCA1, LCAT, CETP and SCARB1 genes); and Disorders associated with low LDL panel (APOB, MTTP, PCSK9, ANGPTL3 and SAR1B genes). We also perform extensive biochemical characterization including TC, C-HDL, C-LDL, TG, apolipoprotein AI, AII, B, CII, CIII, E and sdLDL that enables a better identification of the pathway affect and can direct towards the most suitable molecular study.
- SCARB2 mutations as modifiers in Gaucher disease: the wrong enzyme at the wrong place?Publication . Coutinho, M.F.; Lacerda, L.; Gaspar, A.; Pinto, E.; Ribeiro, I.; Laranjeira, F.; Ribeiro, H.; Silva, E.; Ferreira, C.; Prata, M.J.; Alves, S.Unlike most lysosomal proteins, β-glucocerebrosidase (GCase), the hydrolase defective in Gaucher disease (GD), is delivered to lysosomes through its interaction with the transmembrane protein LIMP2. A few years ago, mutations in its coding gene, SCARB2, were reported to modify the severity of GD phenotype. The existence of a great variety of GD phenotypes is well-known, with numerous patients who carry identical genotypes presenting remarkable phenotypic variability. Over the years, that variability has been attributed to other genetic, epigenetic and/or environmental factors. Still, there is still much to learn on this subject. Recently, an association between Parkinson's disease (PD) and the presence of mutations in the GBA gene has been demonstrated. Moreover, there are also studies suggesting that genetic variants in the SCARB2 gene may also be risk factors for PD. We analysed the SCARB2 gene in the Portuguese cohort of 91 GD patients, having identified 3 different SCARB2 coding variants. Of those, 2 were known polymorphisms with high prevalence in the normal population (p.M159V and p.V396I) and the third was a novel coding variant, p.T398M, present in heterozigousity in a single patient. Our study demonstrated that, at least for the Portuguese population, genetic variability at SCARB2 does not account much to the GD phenotypic spectrum. Nevertheless, in vitro analyses of the novel p.T398M are envisaged, in order to further characterize the effect of this variant on the levels and sub-cellular location of GCase. The clinical presentation of the patient harbouring this coding variant will also be discussed.