Characterization of the First PCSK9 Gain of Function Homozygote
| Autor(a) principal: | |
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| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10400.18/3277 |
Resumo: | Letter |
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Characterization of the First PCSK9 Gain of Function HomozygoteFamilial HypercholesterolemiaHomozygotePCSK9PCSK9 protein, humanDNA/geneticsDNAPortugalDoenças Cardio e Cérebro-vascularesHipercolesterolemia FamiliarLetterGain of function (GOF) mutations in proprotein convertase subtilisin kexin type 9 (PCSK9) are a rare cause of familial hypercholesterolemia (FH). We identified a child with a clinical diagnosis of FH with 2 novel putative PCSK9 GOF missense variants (p.[(Ala62Asp)]; [(Pro467Ala)]), and no mutation in the low-density lipoprotein (LDL) receptor (LDLR) or in apolipoprotein B100 (APOB) genes. The proband was referred to the Portuguese FH Study (1) at age 11 and presented a total cholesterol of 316 mg/dl and low-density lipoprotein cholesterol (LDL-C) of 234 mg/dl on a strict diet. The phenotype presented by all PCSK9 heterozygous carriers within this large pedigree is similar to APOB heterozygous carriers (LDL-C, 198.75 ± 14.98 mg/dl vs. LDL-C, 211.57 ± 42.02 mg/dl; p = 0.227) but significantly different than heterozygous LDLR carriers (LDL-C, 198.75 ± 14.98 mg/dl vs. LDL-C, 230.63 ± 76.50 mg/dl; p = 0.012) when comparing the relatives’ phenotype in our cohort.Funding was obtained from the Portuguese Science and Technology Foundation (FCT) (PTDC/SAU-GMG/101874/2008) (to Dr. Bourbon), from the Spanish Ministry of Economy and Competitiveness (grant N° BFU 2012-36241) and Programa INNPACTO (grant N° IPT-2011-0817-010000) (to Dr. Martin), and from the Agence Nationale de la Recherche (Programme Blanc BCNCT) (to Dr. Lambert). Dr. Alves was a recipient of a PhD grant SFRH/BD/27990/2006 and research grant PTDC/SAU-GMG/101874/2008 from FCT. Mrs. Medeiros was supported by a research grant from the National Institute of Health Doutor Ricardo Jorge (BRJ-DPS/2012). Mr. Benito-Vicente was supported by a grant PIF (2014/2015) Gobierno Vasco. Alirocumab was obtained from Sanofi-Regeneron. Dr. Lambert has received honoraria from Sanofi-Regeneron, Amgen, and Pfizer and research funding from Sanofi-Regeneron. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Alves and Etxebarria contributed equally to this work.Elsevier/ American College of Cardiology FoundationRepositório Científico do Instituto Nacional de SaúdeAlves, Ana CatarinaEtxebarria, AitorMedeiros, Ana MargaridaBenito-Vicente, AsierThedrez, AuréliePassard, MaximeCroyal, MikaëlMartin, CesarLambert, GillesBourbon, Mafalda2016-02-02T16:41:13Z2015-11-102015-11-10T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/3277engJ Am Coll Cardiol. 2015 Nov 10;66(19):2152-4. doi: 10.1016/j.jacc.2015.08.871. Epub 2015 Nov 2.2045-232210.1016/j.jacc.2015.08.871info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:39:47Zoai:repositorio.insa.pt:10400.18/3277Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:38:19.197226Repositório 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 |
Characterization of the First PCSK9 Gain of Function Homozygote |
| title |
Characterization of the First PCSK9 Gain of Function Homozygote |
| spellingShingle |
Characterization of the First PCSK9 Gain of Function Homozygote Alves, Ana Catarina Familial Hypercholesterolemia Homozygote PCSK9 PCSK9 protein, human DNA/genetics DNA Portugal Doenças Cardio e Cérebro-vasculares Hipercolesterolemia Familiar |
| title_short |
Characterization of the First PCSK9 Gain of Function Homozygote |
| title_full |
Characterization of the First PCSK9 Gain of Function Homozygote |
| title_fullStr |
Characterization of the First PCSK9 Gain of Function Homozygote |
| title_full_unstemmed |
Characterization of the First PCSK9 Gain of Function Homozygote |
| title_sort |
Characterization of the First PCSK9 Gain of Function Homozygote |
| author |
Alves, Ana Catarina |
| author_facet |
Alves, Ana Catarina Etxebarria, Aitor Medeiros, Ana Margarida Benito-Vicente, Asier Thedrez, Aurélie Passard, Maxime Croyal, Mikaël Martin, Cesar Lambert, Gilles Bourbon, Mafalda |
| author_role |
author |
| author2 |
Etxebarria, Aitor Medeiros, Ana Margarida Benito-Vicente, Asier Thedrez, Aurélie Passard, Maxime Croyal, Mikaël Martin, Cesar Lambert, Gilles Bourbon, Mafalda |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
| dc.contributor.author.fl_str_mv |
Alves, Ana Catarina Etxebarria, Aitor Medeiros, Ana Margarida Benito-Vicente, Asier Thedrez, Aurélie Passard, Maxime Croyal, Mikaël Martin, Cesar Lambert, Gilles Bourbon, Mafalda |
| dc.subject.por.fl_str_mv |
Familial Hypercholesterolemia Homozygote PCSK9 PCSK9 protein, human DNA/genetics DNA Portugal Doenças Cardio e Cérebro-vasculares Hipercolesterolemia Familiar |
| topic |
Familial Hypercholesterolemia Homozygote PCSK9 PCSK9 protein, human DNA/genetics DNA Portugal Doenças Cardio e Cérebro-vasculares Hipercolesterolemia Familiar |
| description |
Letter |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015-11-10 2015-11-10T00:00:00Z 2016-02-02T16:41:13Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/3277 |
| url |
http://hdl.handle.net/10400.18/3277 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
J Am Coll Cardiol. 2015 Nov 10;66(19):2152-4. doi: 10.1016/j.jacc.2015.08.871. Epub 2015 Nov 2. 2045-2322 10.1016/j.jacc.2015.08.871 |
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info:eu-repo/semantics/embargoedAccess |
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embargoedAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier/ American College of Cardiology Foundation |
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Elsevier/ American College of Cardiology Foundation |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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