Teste Repositóri
2014-01-01
Resultados de pesquisa
Foram encontrados 87 registos.
Familial hypercholesterolemia (FH) results from defects in the hepatic uptake and degradation of LDL via the LDL-receptor pathway, common caused by a loss-of-function mutation in the LDLR receptor gene (LDLR), by mutations in the gene enconding apolipoprotein B (APOB) or rare dominant gain-of-function mutations in a member of the proprotein convertase family (PCSK9). However, mutations which encodes a protein required for clathrin-mediated internalization of the LDLR (LDLRAP1) by the liver, has also been described as a recessive form of FH. The presence of mutations in other genes (CYP7A1, enzyme that catalyses the first step in the hepatic catabolism of cholesterol, and SREBP-2, a transcription factor that bind to the sterol regulatory element ) have been described, but these are very rare causes of hypercholesterolaemia.
In the Por...
Familial hypercholesterolemia (FH) is a genetic condition characterized by a high cholesterol concentration in the blood. The most frequent causes of FH are inherited defects in the Low Density Lipoprotein Receptor gene (LDLR) but, in a small percentage of patients, mutations in the apolipoprotein B gene (APOB) and in the propotein convertase subtilisin/kexin type 9 gene (PCSK9) are also responsible for FH. These 3 genes are currently studied in the “Portuguese FH study”. From the 404 families with a clinical diagnosis of FH already studied only 48% of these have a mutation in one of the 3 studied genes, so other gene defects must exist to explain the cause of hypercholesterolemia in the remaining families.
The first aim was the exclusion of previously unidentified LDLR and APOB gene defects, as well as the exclusion of mutations in ...
Familial hypercholesterolemia (FH) is a genetic condition characterized by a high cholesterol concentration in the blood. The most frequent causes of FH are inherited defects in the Low Density Lipoprotein Receptor gene (LDLR) but, in a small percentage of patients, mutations in the apolipoprotein B gene (APOB) and in the propotein convertase subtilisin/kexin type 9 gene (PCSK9) are also responsible for FH. These 3 genes are currently studied in the “Portuguese FH study”. From the 563 families with a clinical diagnosis of FH studied only 41% of these have a mutation in one of the 3 studied genes, so other gene defects must exist to explain the cause of hypercholesterolemia in the remaining families.
The aim of this study was the exclusion of previously unidentified LDLR and APOB gene defects in 65 severely affected patients, as well ...
Familial hypercholesterolemia (FH) is a genetic condition characterized by a high cholesterol concentration in the blood. The most frequent causes of FH are inherited defects in the Low Density Lipoprotein Receptor gene (LDLR) but, in a small percentage of patients, mutations in the apolipoprotein B gene (APOB) and in the propotein convertase subtilisin/kexin type 9 gene (PCSK9) are also responsible for FH. These 3 genes are currently studied in the “Portuguese FH study”. From the 404 families with a clinical diagnosis of FH already studied only 48% of these have a mutation in one of the 3 studied genes, so other gene defects must exist to explain the cause of hypercholesterolemia in the remaining families.
The first aim was the exclusion of previously unidentified LDLR and APOB gene defects, as well as the exclusion of mutations in ...
Familial hypercholesterolemia (FH) is a monogenic condition caused in most cases by mutations in LDLR gene, but mutations in APOB and PCSK9 genes are also cause of FH. These 3 genes are currently studied in the “Portuguese FH Study”. From the 404 families with a clinical diagnosis of FH studied, only 48% of these have a detectable mutation in the 3 genes mention above so, other mutations in these genes or other gene defects must exist to explain the cause of hypercholesterolemia in the remaining families.
The main aim of this project was the whole sequencing of APOB gene, in 65 index patients with clinical diagnosis of FH, without mutations in LDLR gene or in fragments of exon 26 and 29 of APOB gene, by pyrosequencing, in order to identify the genetic cause of the hypercholesterolemia in these patients.
A pool of the 65 DNAs was se...
Acknowledgements: Ana CatarinaAlves was funded by FCT SFRH / BD / 27990 / 2006 ; project grant FCT_PTDC/SAU-GMG/101874/2008
Familial hypercholesterolemia (FH) results mainly from defects in the hepatic uptake and degradation of LDL via the LDL-receptor pathway, commonly caused by a lossof-function mutation in the LDLR receptor gene (LDLR) or mutations in the gene coding apolipoprotein B (APOB) or rare dominant gain-of-function mutations in a member of the pro-protein convertase family (PCSK9). However, mutations which encode a protein required for clathrin-mediated internalization of the LDLR (LDLRAP1) by the liver, have also been described as a recessive form of FH. The presence of mutations in other genes (CYP7A1, enzyme that catalyses the first step in the hepatic catabolism of cholesterol, and SREBP-2, a transcription factor that binds to the sterol regulatory element) have been described, but as very rare causes of hypercholesterolaemia.
In the Portug...
Identification of young population with high cardiovascular (CV) risk allows early intervention and prevention, delaying or abolishing occurrence of CHD in adult life. Hypercholesterolemia is an important CV risk factor that can be due to environmental or genetic causes. Genetic dyslipidemias, as Familial Hypercholesterolemia (FH), are associated with major risk of CV events.
Hypercholesterolemia is an important cardiovascular risk (CV) factor that can be due to environmental or genetic causes. Identification of a young population with high CV risk allows early intervention and prevention, delaying or abolishing occurrence of CHD in adult life.
Familial Hypercholesterolemia (FH) is associated with major risk of CV events and usually results from mutations in three different genes involved in lipid metabolism such as LDLR, APOB and PCSK9 genes.
The Portuguese FH Study is established in the National Institute of Health, Lisbon, since 1999 where the biochemical characterization and DNA diagnosis have been performed for patients with clinical diagnosis of FH and cascade screening in relatives of the affected index patients.
