{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:14Z","timestamp":1788912014134,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,16]],"date-time":"2020-02-16T00:00:00Z","timestamp":1581811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["BHF PG08\/008"],"award-info":[{"award-number":["BHF PG08\/008"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004001","name":"Guizhou Science and Technology Department","doi-asserted-by":"publisher","award":["PIC\/IC\/83020\/2007"],"award-info":[{"award-number":["PIC\/IC\/83020\/2007"]}],"id":[{"id":"10.13039\/501100004001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004001","name":"Guizhou Science and Technology Department","doi-asserted-by":"publisher","award":["PIC\/IC\/83333\/2007"],"award-info":[{"award-number":["PIC\/IC\/83333\/2007"]}],"id":[{"id":"10.13039\/501100004001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Familial hypercholesterolaemia (FH) is a monogenic disorder characterised by high low\u2010density lipoprotein cholesterol (LDL\u2010C) concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH\u2010causing variant is only found in 40%\u201050% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Between 1999 and 2017, 731 index patients (311 children and 420 adults) who met the Simon Broome diagnostic criteria had been referred to our laboratory.\n                    <jats:italic>LDLR<\/jats:italic>\n                    ,\n                    <jats:italic>APOB<\/jats:italic>\n                    ,\n                    <jats:italic>PCSK9<\/jats:italic>\n                    ,\n                    <jats:italic>APOE<\/jats:italic>\n                    ,\n                    <jats:italic>LIPA<\/jats:italic>\n                    ,\n                    <jats:italic>LDLRAP1<\/jats:italic>\n                    ,\n                    <jats:italic>ABCG5<\/jats:italic>\n                    \/8 genes were analysed by polymerase chain reaction amplification and Sanger sequencing. The 6\u2010SNP LDL\u2010C genetic risk score (GRS) for polygenic hypercholesterolaemia was validated in the Portuguese population and cases with a GRS over the 25th percentile were considered to have a high likelihood of polygenic hypercholesterolaemia. An FH\u2010causing mutation was found in 39% of patients (94% in\n                    <jats:italic>LDLR<\/jats:italic>\n                    , 5%\n                    <jats:italic>APOB<\/jats:italic>\n                    and 1%\n                    <jats:italic>PCSK9<\/jats:italic>\n                    ), while at least 29% have polygenic hypercholesterolaemia and 1% have other lipid disorders. A genetic cause for the FH phenotype was found in 503 patients (69%). All known causes of the FH phenotype should be investigated in FH cohorts to ensure accurate diagnosis and appropriate management.\n                  <\/jats:p>","DOI":"10.1111\/cge.13697","type":"journal-article","created":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T22:00:06Z","timestamp":1577829606000},"page":"457-466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["The familial hypercholesterolaemia phenotype: Monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes"],"prefix":"10.1111","volume":"97","author":[{"given":"Cibelle","family":"Mariano","sequence":"first","affiliation":[{"name":"Cardiovascular Research Group, Research and Development Unit, Department of Health Promotion and Chronic Diseases National Institute of Health Doutor Ricardo Jorge  Lisbon Portugal"},{"name":"Faculty of Sciences, BioISI \u2013 Biosystems &amp; Integrative Sciences Institute 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Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana Rita","family":"Chora","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Group, Research and Development Unit, Department of Health Promotion and Chronic Diseases National Institute of Health Doutor Ricardo Jorge  Lisbon Portugal"},{"name":"Faculty of Sciences, BioISI \u2013 Biosystems &amp; Integrative Sciences Institute University of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00edlia","family":"Antunes","sequence":"additional","affiliation":[{"name":"Department of Statistics and Operations Research, Faculty of Sciences University of Lisbon  Lisbon Portugal"},{"name":"Centre of Statistics and its Applications \u2013 CEAUL, Faculty of Sciences University of Lisbon  Lisbon Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Futema","sequence":"additional","affiliation":[{"name":"Centre for Heart 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