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Global Survey Of Genetic Testing Methods For Familial Hypercholesterolaemia: A Study And Recommendations From The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration Registry

2026-05-14Artigo científico Acesso aberto
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datacite.subject.fosCiências Médicas
dc.contributor.authorChora, Joana Rita
dc.contributor.authorKarungi, Irene
dc.contributor.authorElshorbagy, Amany
dc.contributor.authorStevens, Christophe A.T.
dc.contributor.authorVallejo-Vaz, Antonio J.
dc.contributor.authorDharmayat, Kanika I.
dc.contributor.authorAbifadel, Marianne
dc.contributor.authorAguilar-Salinas, Carlos A.
dc.contributor.authorAlhabib, Khalid F.
dc.contributor.authorAlmahmeed, Wael
dc.contributor.authorAlnouri, Fahad
dc.contributor.authorAlonso, Rodrigo
dc.contributor.authorAl-Rasadi, Khalid
dc.contributor.authorAl-Sarraf, Ahmad
dc.contributor.authorArca, Marcello
dc.contributor.authorAshaat, Engy A.
dc.contributor.authorAshavaid, Tester F.
dc.contributor.authorAverna, Maurizio
dc.contributor.authorBanach, Maciej
dc.contributor.authorBecker, Marianne
dc.contributor.authorBinder, Christoph J.
dc.contributor.authorBrunham, Liam R.
dc.contributor.authorCatapano, Alberico L.
dc.contributor.authorCorral, Pablo
dc.contributor.authorDescamps, Olivier S.
dc.contributor.authorDrogari, Euridiki
dc.contributor.authorDurst, Ronen
dc.contributor.authorEzhov, Marat
dc.contributor.authorGroselj, Urh
dc.contributor.authorHarada-Shiba, Mariko
dc.contributor.authorHolven, Kirsten B.
dc.contributor.authorHovingh, G. Kees
dc.contributor.authorKhovidhunkit, Weerapan
dc.contributor.authorLalic, Katarina
dc.contributor.authorLatkovskis, Gustavs
dc.contributor.authorLaufs, Ulrich
dc.contributor.authorLiberopoulos, Evangelos
dc.contributor.authorLin, Jie
dc.contributor.authorMärz, Winfried
dc.contributor.authorMata, Pedro
dc.contributor.authorMatthias, Anne Thushara
dc.contributor.authorMiserez, André R.
dc.contributor.authorMitchenko, Olena
dc.contributor.authorNawawi, Hapizah Mohd
dc.contributor.authorNordestgaard, Børge G.
dc.contributor.authorPanayiotou, Andrie G.
dc.contributor.authorParagh, György
dc.contributor.authorPetrulioniene, Zaneta
dc.contributor.authorPostadzhiyan, Arman
dc.contributor.authorReyes, Ximena
dc.contributor.authorSadiq, Fouzia
dc.contributor.authorSahebkar, Amirhossein
dc.contributor.authorSantos, Raul D.
dc.contributor.authorSawhney, J.P.S.
dc.contributor.authorSchunkert, Heribert
dc.contributor.authorShah, Swarup A.V.
dc.contributor.authorShek, Aleksandr B.
dc.contributor.authorSoran, Handrean
dc.contributor.authorSu, Ta-Chen
dc.contributor.authorSubramaniam, Tavintharan
dc.contributor.authorTilney, Myra
dc.contributor.authorTomlinson, Brian
dc.contributor.authorTruong, Thanh Huong
dc.contributor.authorTybjærg-Hansen, Anne
dc.contributor.authorViigimaa, Margus
dc.contributor.authorVohnout, Branislav
dc.contributor.authorWatts, Gerald F.
dc.contributor.authorYamashita, Shizuya
dc.contributor.authorRay, Kausik K.
dc.contributor.authorRaal, Frederick J.
dc.contributor.authorHumphries, Steve E.
dc.contributor.authorFreiberger, Tomas
dc.contributor.authorBourbon, Mafalda
dc.contributor.authorEAS FHSC
dc.date.accessioned2026-10-07T09:31:03Z
dc.date.available2026-10-07T09:31:03Z
dc.date.issued2026-05-14
dc.descriptionContributors to Country Data for Current Study - PORTUGAL: Ana Margarida Medeiros (Instituto Nacional de Saúde Doutor Ricardo Jorge, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis Unidade de I&D, Grupo de Investigação Cardiovascular, Lisboa), Ana Catarina Alves (Instituto Nacional de Saúde Doutor Ricardo Jorge, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis Unidade de I&D, Grupo de Investigação Cardiovascular, Lisboa), Beatriz Miranda (Instituto Nacional de Saúde Doutor Ricardo Jorge, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis Unidade de I&D, Grupo de Investigação Cardiovascular, Lisboa).
dc.description.abstractBackground and aims: Familial hypercholesterolemia (FH), primarily caused by pathogenic LDLR, APOB, or PCSK9 variants, results in elevated LDL-C and increased cardiovascular risk. Genetic testing offers the definitive diagnosis, yet global approaches to FH genetic testing remain unstandardized. We investigate current testing practices worldwide and provide relevant recommendations. Methods: A survey was distributed to national lead-investigators (NLIs) of 68 countries in the FH-Studies Collaboration, assessing referral criteria, assay methodologies, target genes, and pathogenicity interpretation methods. Results: NLIs from centres in 55/68 countries (81%) responded, spanning Africa (N=2), Americas (N=6), Asia (N=20), Europe (N=26), and Oceania (N=1). DLCN scores were the most common reason for referral to genetic testing (adults:72%; children:57%). Simon Broome and MEDPED criteria were reported only by centres from high-income countries (adults: 7% and 2%; children: 12% and 2%). Methods for testing in index versus non-index cases were significantly different (p <0.001). Next-generation sequencing (NGS) was the predominant assay method for index cases (62%), while Sanger sequencing was favoured for non-index (71%). However, these testing techniques did not differ between centres from high- and non-high-income countries for index cases (p=0.74) and non-index cases (p=0.49). Copy-number variants (CNVs) were assessed by 65% of centres, with most integrating CNV analysis into NGS platforms (86%) and others (14%) using multiplex ligation-dependent probe-amplification (MLPA) or microarrays. Screening encompassed LDLR (100%), APOB (97%), PCSK9 (95%), and other genes. Most centres (96%) incorporated pathogenicity interpretation into their reports, adhering largely to American College of Medical Genetics and Genomics guidelines. Conclusions: FH genetic testing practices vary widely across countries surveyed, emphasizing the need for global standardization to enhance accuracy and comparability of FH diagnoses worldwide. We suggest that genetic testing should include the three FH-causing genes and ideally the five associated/phenocopy genes.eng
dc.description.abstractLay Summary: This was a global survey from centres within 55 countries within the Familial Hypercholesterolemia Studies Collaboration (FHSC). The study evaluated the current practice of genetic testing for familial hypercholesterolemia (FH), an inherited condition characterized by high cholesterol levels and increased cardiovascular risk, since a definitive diagnosis is a key determinant of patient-centred care. The study found that while most centres screen for the three main FH genes and incorporate interpretation on whether a genetic change is disease-causing, notable differences existed in the reasons for referring for a test and laboratory testing techniques among and within centres from high and non-high income countries. Among testing techniques, next-generation sequencing was the predominant method for testing index cases, while Sanger sequencing was commonly used for relatives. The study also found that about one-third of centres did not test for other important genetic changes called copy-number variants (CNVs).To ensure patients receive accurate diagnoses regardless of where they live, the authors recommend creating a global standard where testing always includes the three primary genes responsible for the condition, ideally alongside five other associated genes.eng
dc.description.sponsorshipMafalda Bourbon acknowledges research grants from EU Horizon RIA: 101155885-2, FH-EARLY and La Caixa Foundation (LCF/PR/HP23/52330032).
dc.identifier.citationEur J Prev Cardiol. 2026 May 14:zwag198. doi: 10.1093/eurjpc/zwag198. Online ahead of print
dc.identifier.doi10.1093/eurjpc/zwag198
dc.identifier.eissn2047-4881
dc.identifier.issn2047-4873
dc.identifier.pmid42133473
dc.identifier.urihttp://hdl.handle.net/10400.18/11378
dc.language.isoeng
dc.peerreviewedyes
dc.publisherOxford University Press
dc.relationNEW STRATEGIES FOR THE EARLY DIAGNOSIS, RISK STRATIFICATION AND CO-MANAGEMENT OF FAMILIAL HYPERCHOLESTEROLEMIA
dc.relation.hasversionhttps://academic.oup.com/eurjpc/advance-article/doi/10.1093/eurjpc/zwag198/8678229
dc.relation.ispartofEuropean Journal of Preventive Cardiology
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectFamilial Hypercholesterolemia
dc.subjectGenetic Testing
dc.subjectGenetics
dc.subjectGlobal Standardization
dc.subjectPathogenicity Interpretation
dc.subjectDoenças Cardio e Cérebro-vasculares
dc.subjectDoenças Genéticas
dc.titleGlobal Survey Of Genetic Testing Methods For Familial Hypercholesterolaemia: A Study And Recommendations From The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration Registryeng
dc.typejournal article
dcterms.referenceshttps://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/eurjpc/PAP/10.1093_eurjpc_zwag198/2/zwag198_supplementary_data.zip?Expires=1785494547&Signature=nu2br~Y3pNGuPLsGQ2PKfyRldRxEvL-943HeTR54~vuFRcvmD97YobkJZLCuMkKxOWTFVhjxl8V14DDoDFXOInMMwD4wglOnGdZpeGAD0QHVdNklNg3T~RFE~fRY3VmsC01ZgTlfYWFwtyemF2AL26PyJjtv6fDyh1fznhdJhvPOWnlMn-9p-iNzICrDMKzWfFiA50hzOvHVv6nUb~JQ~5g-zT60bo3B0Rf0I6qNFjJ~L35DlWX~irMMPywhpUTcgdKXL2EBXW7LWQ7tY0lrXpwDqR6IhemGY~GyJjnAqq4mX9oGXF0KG18ufEofQ6FJTYcL~nEC~Kh6Wij~j-FwXw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
dcterms.referenceshttps://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/eurjpc/PAP/10.1093_eurjpc_zwag198/2/zwag198_supplementary_data.zip?Expires=1785494547&Signature=nu2br~Y3pNGuPLsGQ2PKfyRldRxEvL-943HeTR54~vuFRcvmD97YobkJZLCuMkKxOWTFVhjxl8V14DDoDFXOInMMwD4wglOnGdZpeGAD0QHVdNklNg3T~RFE~fRY3VmsC01ZgTlfYWFwtyemF2AL26PyJjtv6fDyh1fznhdJhvPOWnlMn-9p-iNzICrDMKzWfFiA50hzOvHVv6nUb~JQ~5g-zT60bo3B0Rf0I6qNFjJ~L35DlWX~irMMPywhpUTcgdKXL2EBXW7LWQ7tY0lrXpwDqR6IhemGY~GyJjnAqq4mX9oGXF0KG18ufEofQ6FJTYcL~nEC~Kh6Wij~j-FwXw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
dspace.entity.typePublication
oaire.awardNumber101155885
oaire.awardTitleNEW STRATEGIES FOR THE EARLY DIAGNOSIS, RISK STRATIFICATION AND CO-MANAGEMENT OF FAMILIAL HYPERCHOLESTEROLEMIA
oaire.awardURIhttp://hdl.handle.net/10400.18/11377
oaire.citation.startPagezwag198
oaire.citation.titleEuropean Journal of Preventive Cardiology
oaire.fundingStreamHORIZON Research and Innovation Actions
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
relation.isProjectOfPublication1bd42dfc-99a7-4cce-9743-191d748e857f
relation.isProjectOfPublication.latestForDiscovery1bd42dfc-99a7-4cce-9743-191d748e857f

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