Browsing by Author "Medeiros, A."
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- Complex phenotype of hypercholesterolaemia in a family with both ABCG8 and APOB mutationsPublication . Padeira, G.; Gomes, I.; Correia, C.; Valongo, C.; Alves, A.C.; Medeiros, A.; Bourbon, M.; Ferreira, A.C.Familial Hypercholesterolemia (FH) is the most common of all genetic hypercholesterolaemias with defects in LDLR, APOB and PCSK9 accounting for the majority of cases. However, there are other rare disorders like sitosterolaemia that can present the same phenotype. Both can cause premature atherosclerosis but have distinctive dietetic and therapeutic intervention.
- Dislipidemia hereditária VS dislipidemia ambiental em crianças portuguesasPublication . Medeiros, A.; Alves, A.C.; Bourbon, M.A hipercolesterolemia é um importante factor de risco cardiovascular (CV) cuja origem pode ser ambiental ou genética. A identificação de uma população jovem com elevado risco CV permite uma intervenção precoce, adiando ou suprimindo a ocorrência de doença cardiovascular na vida adulta. A Hipercolesterolemia Familiar (FH) está associada a um elevado risco CV e resulta de mutações em três genes do metabolismo dos lípidos: LDLR, APOB e PCSK9. O Estudo Português de Hipercolesterolemia Familiar (EPHF) realiza a identificação genética de doentes com diagnóstico clinico de FH. O objectivo deste estudo é distinguir entre FH e uma dislipidemia de origem ambiental num grupo de crianças que apresentam o mesmo diagnóstico.
- Frequency and clinical and molecular aspects of familial hypercholesterolemia in an endocrinology unit in Ciudad Bolívar, VenezuelaPublication . Lima-Martínez, M.M.; Paoli, M.; Vázquez-Cárdenas, A.; Magaña-Torres, M.T.; Guevara, O.; Muñoz, M.C.; Parrilla-Alvarez, A.; Márquez, Y.; Medeiros, A.; Bourbon, M.OBJECTIVE: To assess the frequency and the clinical, biochemical, and molecular aspects of familial hypercholesterolemia (FH) in subjects attending an endocrinology unit. METHODS: An observational, descriptive study evaluating 3,140 subjects attending the endocrinology unit of Centro Médico Orinoco in Ciudad Bolívar, Venezuela, from 7 January 2013 to 9 December 2016. The index cases were selected using the Dutch Lipid Clinic Network criteria. Plasma lipid levels were measured, and a molecular analysis was performed by DNA sequencing of the LDLR and APOB genes. RESULTS: Ten (0.32%) of the 3,140 study patients had clinical and biochemical characteristics consistent with FH. All but one were female. Three had first-degree relatives with prior premature coronary artery; and none had a personal history of this condition. Three patients were obese; three had high blood pressure; and no one suffered from diabetes. Three patients had a history of tendon xanthomas, and one of corneal arcus. LDL-C levels ranged from 191 to 486mg/dL. Two patients were on statin therapy. The genetic causes of FH were identified in four patients, and were LDLR gene mutations in three of them and an APOB gene mutation in exon 26 in the other. CONCLUSION: Approximately, one out of every 300 people attending this endocrinology unit in those four years had FH, and LDLR gene mutations were the most prevalent cause.
- Functional Genomics in a cohort of FH mutation negative patientsPublication . Rossi, N.; Graça, R.; Alves, A.C.; Medeiros, A.; Zimon, M.; Rausch, T.; Benes, V.; Pepperkok, R.; Bourbon, M.Background: Clinically, Familial Hypercholesterolaemia (FH) is characterized by high plasma concentrations of total and LDL cholesterol from birth, leading to premature atherosclerosis and coronary heart disease. Currently, the genetic diagnosis is made by finding a functional mutation in one of 3 genes: low-density lipoprotein receptor (LDLR ≈ 90-94%), apolipoprotein B (APOB ≈ 5-9%) and proprotein convertase subtilisin/kexin type 9 (PCSK9 ≈ 1-3%). Problem: Worldwide 50% of clinically diagnosed FH patients lack the identification of a causative mutation to explain their phenotype. Aim: Explore if rare genetic variants in genes involved in monogenic forms of dyslipidaemia can contribute to the FH phenotype.
- Improving familial dyslipidaemia diagnosisPublication . Graça, R.; Rossi, N.; Alves, A.C.; Medeiros, A.; Zimon, M.; Raush, T.; Benes, V.; Pepperkok, R.; Bourbon, M.Aim: Familial Hypercholesterolemia (FH) is characterized clinically by high LDL plasma concentrations from birth leading to premature atherosclerosis and CHD. Only 40% of the patients enrolled in the Portuguese FH Study carry a putative pathogenic mutation. The remaining individuals may have polygenic forms of dyslipidaemia or mutations in genes not yet associated with FH.
- O método de cascade screening na identificação de doentes com hipercolesterolemia familiarPublication . Medeiros, A.; Leitão, F.; Alves, A.C.; Bourbon, M.A Hipercolesterolemia Familiar (FH) é uma doença genética do metabolismo lipídico causada por mutações nos genes LDLR, APOB e PCSK9. Caracteriza-se clinicamente por níveis elevados de colesterol LDL, que se vão depositando nas artérias conduzindo ao desenvolvimento de doenças cardiovasculares prematuras. De acordo com a frequência europeia (1:500) estima-se que existam cerca de 20.000 indivíduos afectados com FH em Portugal, mas a doença encontra-se sub-diagnosticada no nosso país. O método Cascade Screening (CS) permite a identificação de novos casos com FH através do estudo molecular de vários indivíduos de uma família identificada previamente com FH. O objectivo deste trabalho é estabelecer a importância do método de CS na identificação de novos casos de FH, que de outro modo não seria identificados.
- Perfil de risco cardiovascular de estudantes do ensino secundárioPublication . Rocha, T.; Alves, A.; Medeiros, A.; Francisco, V.; Silva, S.; Guiomar, S.; Paixão, E.; Gaspar, I.; Rato, Q.; Bourbon, M.
- Sitosterolémia - uma causa rara de uma situação comumPublication . Garcia, A.M.; Padeira, G.; Conde, M.; Carvalho, R.; João, A.; Gomes, I.; Bosquet, Lucas G.; Correia, C.; Valongo, C.; Dias, A.; Medeiros, A.; Bourbon, Mafalda; Ferreira, A.C.Introdução: A Sitosterolémia (OMIM 210250) é uma doença autossómica recessiva rara do metabolismo dos esteróis vegetais. É causada por mutações nos genes ABCG5 ou ABCG8 (2p21) que codificam as proteínas esterolina 1 e 2 do transportador ABC (ATP-binding cassette), com consequente comprometimento da excreção intestinal e biliar de esteróis e sua acumulação no sangue e tecidos. Clinicamente é caracterizada pela presença de xantomas, níveis elevados de colesterol e aterosclerose prematura, fazendo diagnóstico diferencial com a Hipercolesterolémia Familiar.
- The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causesPublication . Mariano, C.; Alves, A.C.; Medeiros, A.; Chora, J.R.; Antunes, M.; Futema, M.; Humphries, S.E.; Bourbon, M.Familial Hypercholesterolaemia (FH) is a monogenic disorder characterised by high LDL-C concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH-causing variant is only found in 40-50% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Methods and Results Between 1999 and 2017, 731 index patients (311 children and 420 adults) who met the Simon Broome diagnostic criteria had been referred to our laboratory. LDLR, APOB, PCSK9, APOE, LIPA, LDLRAP1, ABCG5/8 genes were analysed by PCR amplification and Sanger sequencing. The 6-SNP LDL-C genetic risk score (GRS) for polygenic hypercholesterolaemia was validated in the Portuguese population and cases with a GRS over the 25th percentile were considered to have a high likelihood of polygenic hypercholesterolaemia. An FH-causing mutation was found in 39% of patients (94% in LDLR, 5% APOB and 1% PCSK9), while at least 29% have polygenic hypercholesterolaemia and 1% have other lipid disorders. A genetic cause for the FH phenotype was found in 503 patients (69%). All known causes of the FH phenotype should be investigated in FH cohorts to ensure accurate diagnosis and appropriate management.