Publication
ClassificaĆ§Ć£o de variantes de hipercolesterolemia familiar pelo painel de peritos do Clinical Genome Resource
| dc.contributor.author | Chora, Joana Rita | |
| dc.contributor.author | Bourbon, Mafalda | |
| dc.contributor.author | em nome do FH Variant Curation Expert Panel | |
| dc.date.accessioned | 2024-06-26T09:52:01Z | |
| dc.date.available | 2024-06-26T09:52:01Z | |
| dc.date.issued | 2024-04 | |
| dc.description.abstract | hipercolesterolemia familiar (FH) Ć© a patologia monogĆ©nica mais comum e caracteriza-se por valores muito elevados de colesterol em circulaĆ§Ć£o, levando Ć sua deposiĆ§Ć£o nas artĆ©rias e causando aterosclerose prematura. IndivĆduos com FH tĆŖm variantes patogĆ©nicas, principalmente no gene LDLR (>90%), mas tambĆ©m nos genes APOB e PCSK9, genes estes muito importantes no metabolismo lipĆdico. O diagnĆ³stico genĆ©tico Ć© o diagnĆ³stico definitivo, mas existem atualmente mais de 3500 variantes diferentes no LDLR listadas na ClinVar, e no inĆcio deste trabalho, 565 apresentavam classificaƧƵes conflituosas de patogenicidade, nĆ£o permitindo assim confirmar o diagnĆ³stico clĆnico nos indivĆduos portadores destas variantes. Neste trabalho apresentamos o progresso da classificaĆ§Ć£o de variantes no LDLR pelo FH Variant Curation Expert Panel (VCEP) do Clinical Genome Resource (ClinGen), segundo a recomendaĆ§Ć£o publicada pelo mesmo grupo para classificaĆ§Ć£o de variantes no gene LDLR. No processo de classificaĆ§Ć£o das variantes no gene LDLR, laboratĆ³rios associados enviam dados internos de casos Ćndex com a variante em estudo, que sĆ£o colocados no Variant Curation Interface e complementados com evidĆŖncias publicadas em artigos cientĆficos e outros dados obtidos de outras bases de dados como descrito na recomendaĆ§Ć£o. Cada variante Ć© avaliada por um biocurador sĆ©nior ou dois juniores e aprovada por trĆŖs revisores antes de ser publicada oficialmente na ClinVar. Atualmente avaliĆ”mos 531 variantes no gene LDLR. O FH VCEP classificou 5% destas variantes como benignas/provavelmente benignas, 39% como patogĆ©nicas/provavelmente patogĆ©nicas, 48% como variantes de significado incerto, 1% como conflituosas e 7% estĆ£o ainda em avaliaĆ§Ć£o. As classificaƧƵes definitivas aumentaram de 34% para 44%, e as classificaƧƵes conflituosas diminuĆram de 56% para 1%. O trabalho do FH VCEP visa melhorar o diagnĆ³stico genĆ©tico da FH, para o qual a classificaĆ§Ć£o correta das variantes no LDLR Ć© de extrema importĆ¢ncia. As recomendaƧƵes do FH VCEP diminuem significativamente as classificaƧƵes conflituosas, melhorando o diagnĆ³stico da FH no mundo inteiro. | pt_PT |
| dc.description.abstract | Familial hypercholesterolemia (FH) is the most common monogenic disorder and is characterized by very high levels of circulating cholesterol, leading to its deposition in ar teries and causing premature atherosclerosis. Individuals with FH have pathogenic variants, mainly in LDLR gene (>90%), but also in APOB and PCSK9 genes, which are highly impor tant genes in lipid metabolism. Genetic diagnosis is the definite diagnosis, but there are currently over 3500 different variants in LDLR listed in ClinVar and, at the beginning of this work, 565 had conflicting classifications of pathogenicity, thus not confirming the clinical diagnosis in individuals carrying these variants. In this work, we present the progress of LDLR variant classification by the Clinical Genome Resourceās (ClinGen) FH Variant Curation Expert Panel (VCEP), according to the LDLR consensus variant classification recommendations published by said group. In the process of classifying LDLR variants, associated labs send internal data on index cases with the variants under study, which is uploaded into the Variant Curation Interface (VCI) and supplemented by evidence published in literature and data obtained from other databases, as described in the recommendations. Each variant is assessed by one senior or two junior biocurators and approved by three reviewers before being officially published to ClinVar. We have currently evaluated 531 LDLR variants. FH VCEP classified 5% of the variants as benign/likely benign, 39% as pathogenic/likely pathogenic, 48% as variants of uncertain significance, 1% as conflicting and 7% are still under evaluation. Definite classifications increased from 34% to 44%, and conflicting classifications decreased from 56% to 1%. Efforts of the FH VCEP aim to improve FH genetic diagnosis, for which the correct LDLR variant classification is of utmost importance. FH VCEPās recommendations significantly decrease conflicting classifications, improving the diagnosis of FH worldwide. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | Boletim EpidemiolĆ³gico ObservaƧƵes. 2024 janeiro-abril;13(35):73-79 | pt_PT |
| dc.identifier.issn | 0874-2928 | |
| dc.identifier.issn | 2182-8873 (em linha) | |
| dc.identifier.uri | http://hdl.handle.net/10400.18/9181 | |
| dc.language.iso | por | pt_PT |
| dc.publisher | Instituto Nacional de SaĆŗde Doutor Ricardo Jorge, IP | pt_PT |
| dc.subject | Hipercolesterolemia Familiar | pt_PT |
| dc.subject | Colesterol | pt_PT |
| dc.subject | ClassificaĆ§Ć£o de Variantes | pt_PT |
| dc.subject | Clinical Genome Resource | pt_PT |
| dc.subject | DoenƧas GenƩticas e CondiƧƵes de Base GenƩtica | pt_PT |
| dc.subject | RecomendaƧƵes | pt_PT |
| dc.title | ClassificaĆ§Ć£o de variantes de hipercolesterolemia familiar pelo painel de peritos do Clinical Genome Resource | pt_PT |
| dc.title.alternative | Familial hypercholesterolemia variant classification by the Clinical Genome Resource expert panel | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Lisboa, Portugal | pt_PT |
| oaire.citation.endPage | 79 | pt_PT |
| oaire.citation.issue | 35 | pt_PT |
| oaire.citation.startPage | 73 | pt_PT |
| oaire.citation.title | Boletim EpidemiolĆ³gico ObservaƧƵes | pt_PT |
| oaire.citation.volume | 13 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |
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