Molecular study of Familial Dyslipidaemias by Next Generation Sequencing

Detalhes bibliográficos
Autor(a) principal: Miranda, Beatriz de Carvalho Vieira Raposo
Data de Publicação: 2022
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/53702
Resumo: Tese de mestrado, Bioquímica (Bioquímica Médica) Universidade de Lisboa, Faculdade de Ciências, 2022
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spelling Molecular study of Familial Dyslipidaemias by Next Generation Sequencingdislipidemia familiarSequenciação de Nova Geração (NGS)diagnóstico molecularvariantesTeses de mestrado - 2022Departamento de Química e BioquímicaTese de mestrado, Bioquímica (Bioquímica Médica) Universidade de Lisboa, Faculdade de Ciências, 2022Dyslipidemia, a clinical condition defined by an abnormal concentration of lipids in the blood, can have a genetic etiology. Familial dyslipidemias constitute a group of genetically determined conditions, the majority being rare. In addition, these are often associated to serious conditions that can be prevented by the early identification of patients. Hypercholesterolemia promotes atherosclerosis, increasing patients' cardiovascular risk. Neurological manifestations and poor weight progression are frequent complications of hypocholesterolemia, and an increased risk of pancreatitis is often verified in cases of hypertriglyceridemia. This project aimed to identify the genetic cause of dyslipidemia in 96 Portuguese individuals, referred to the Cardiovascular Research Group at the National Health Institute, with a clinical diagnosis of several genetic dyslipidemias associated to different traits: hypercholesterolaemia, hypocholesterolaemia, and hypertriglyceridaemia. The lipid profile of the 96 index cases was determined for biochemical characterization. The molecular study of individuals was performed by Next Generation Sequencing with a customised target panel of 57 genes involved in lipid metabolism. Molecular diagnosis was provided after analysis of 18 genes strongly associated with several familial dyslipidemias. Rare variants detected were confirmed by PCR and Sanger Sequencing. A definite cause of monogenic dyslipidemia was established in 35 cases: 22 individuals were diagnosed with familial hypercholesterolaemia, 3 with familial hypobetalipoproteinemia, 2 with familial chylomicronemia syndrome, 7 with multifactorial chylomicronemia, and one with autosomal recessive hypertriglyceridemia. Moreover, several variants with uncertain significance were found by NGS during this project, the majority lacking functional data. As these variants can constitute the cause of disease in some cases, functional studies will be essential to assess variant’s pathogenicity. This work allowed an early and correct identification of Portuguese patients with different familial dyslipidemias, thus providing guidance for pharmacological treatment and lifestyle adaptations to reduce the chance of suffering disease complications, improving this way patients’ prognosis.Bourbon, Mafalda, 1973-Alves, Ana CatarinaRepositório da Universidade de LisboaMiranda, Beatriz de Carvalho Vieira Raposo2022-07-07T09:03:48Z202220222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10451/53702enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:59:42Zoai:repositorio.ul.pt:10451/53702Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:38.067017Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Molecular study of Familial Dyslipidaemias by Next Generation Sequencing
title Molecular study of Familial Dyslipidaemias by Next Generation Sequencing
spellingShingle Molecular study of Familial Dyslipidaemias by Next Generation Sequencing
Miranda, Beatriz de Carvalho Vieira Raposo
dislipidemia familiar
Sequenciação de Nova Geração (NGS)
diagnóstico molecular
variantes
Teses de mestrado - 2022
Departamento de Química e Bioquímica
title_short Molecular study of Familial Dyslipidaemias by Next Generation Sequencing
title_full Molecular study of Familial Dyslipidaemias by Next Generation Sequencing
title_fullStr Molecular study of Familial Dyslipidaemias by Next Generation Sequencing
title_full_unstemmed Molecular study of Familial Dyslipidaemias by Next Generation Sequencing
title_sort Molecular study of Familial Dyslipidaemias by Next Generation Sequencing
author Miranda, Beatriz de Carvalho Vieira Raposo
author_facet Miranda, Beatriz de Carvalho Vieira Raposo
author_role author
dc.contributor.none.fl_str_mv Bourbon, Mafalda, 1973-
Alves, Ana Catarina
Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Miranda, Beatriz de Carvalho Vieira Raposo
dc.subject.por.fl_str_mv dislipidemia familiar
Sequenciação de Nova Geração (NGS)
diagnóstico molecular
variantes
Teses de mestrado - 2022
Departamento de Química e Bioquímica
topic dislipidemia familiar
Sequenciação de Nova Geração (NGS)
diagnóstico molecular
variantes
Teses de mestrado - 2022
Departamento de Química e Bioquímica
description Tese de mestrado, Bioquímica (Bioquímica Médica) Universidade de Lisboa, Faculdade de Ciências, 2022
publishDate 2022
dc.date.none.fl_str_mv 2022-07-07T09:03:48Z
2022
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/53702
url http://hdl.handle.net/10451/53702
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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