{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T12:16:29Z","timestamp":1771676189505,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Familial hypercholesterolaemia (FH) is characterized by increased circulating low-density lipoprotein (LDL) cholesterol leading to premature atherosclerosis and coronary heart disease. Although FH is usually caused by mutations in LDLR, mutations in APOB and PCSK9 also cause FH but only a few mutations have been reported, APOB p.R3527Q being the most common. However, 30\u201380% of clinical FH patients do not present an identifiable mutation in any of the described genes. To identify the genetic cause of the hypercholesterolaemia in 65 patients without mutations in LDLR, PCSK9 or in fragments of exon 26 and 29 of APOB currently analysed, we performed whole sequencing of APOB by pyrosequencing. A total of 10 putative mutations in APOB were identified. Flow cytometry with fluorescently labelled LDL from patients and relatives showed that p.Arg1164Thr (exon 22) and p.Gln4494del (exon 29) presented a 40% decrease in internalization in lymphocytes and HepG2 cells, very similar to APOB3527. The proliferation assays with U937 cells showed reduced growth for both cases. The variant p.Tyr1247Cys was found to be neutral and other three alterations were considered polymorphisms. Our results emphasize the need to study the whole APOB in routine protocols to improve patient identification and cardiovascular risk assessment.<\/jats:p>","DOI":"10.1093\/hmg\/ddt573","type":"journal-article","created":{"date-parts":[[2013,11,15]],"date-time":"2013-11-15T01:16:25Z","timestamp":1384478185000},"page":"1817-1828","source":"Crossref","is-referenced-by-count":76,"title":["Novel functional APOB mutations outside LDL-binding region causing familial hypercholesterolaemia"],"prefix":"10.1093","volume":"23","author":[{"given":"Ana Catarina","family":"Alves","sequence":"first","affiliation":[{"name":"1 \u00a0Unidade de I&D, Grupo de Investiga\u00e7\u00e3o Cardiovascular, Departamento de Promo\u00e7\u00e3o da Sa\u00fade e Preven\u00e7\u00e3o de Doen\u00e7as n\u00e3o Transmiss\u00edveis, Instituto Nacional de Sa\u00fade Dr. Ricardo Jorge, Lisboa, Portugal"},{"name":"2 \u00a0Center for Biodiversity, Functional & Integrative Genomics (BioFIG), Lisboa, Portugal"}]},{"given":"Aitor","family":"Etxebarria","sequence":"additional","affiliation":[{"name":"3 \u00a0Unidad de Biof\u00edsica (CSIC, UPV\/EHU) and Departamento de Bioqu\u00edmica, Universidad del Pa\u00eds Vasco, Bilbao, Spain"}]},{"given":"Anne Katherine","family":"Soutar","sequence":"additional","affiliation":[{"name":"4 \u00a0MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK"}]},{"given":"Cesar","family":"Martin","sequence":"additional","affiliation":[{"name":"3 \u00a0Unidad de Biof\u00edsica (CSIC, UPV\/EHU) and Departamento de Bioqu\u00edmica, Universidad del Pa\u00eds Vasco, Bilbao, Spain"}]},{"given":"Mafalda","family":"Bourbon","sequence":"additional","affiliation":[{"name":"1 \u00a0Unidade de I&D, Grupo de Investiga\u00e7\u00e3o Cardiovascular, Departamento de Promo\u00e7\u00e3o da Sa\u00fade e Preven\u00e7\u00e3o de Doen\u00e7as n\u00e3o Transmiss\u00edveis, Instituto Nacional de Sa\u00fade Dr. Ricardo Jorge, Lisboa, Portugal"},{"name":"2 \u00a0Center for Biodiversity, Functional & Integrative Genomics (BioFIG), Lisboa, Portugal"}]}],"member":"286","published-online":{"date-parts":[[2013,11,13]]},"reference":[{"key":"2022050522002447100_DDT573C1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1126\/science.3513311","article-title":"A receptor-mediated pathway for cholesterol homeostasis","volume":"232","author":"Brown","year":"1986","journal-title":"Science"},{"key":"2022050522002447100_DDT573C2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.33549\/physiolres.930000.50.337","article-title":"Major apolipoprotein B-100 mutations in lipoprotein metabolism and atherosclerosis","volume":"50","author":"Vrabl\u00edk","year":"2001","journal-title":"Physiol. 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Genet."},{"key":"2022050522002447100_DDT573C6","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/iub.299","article-title":"Rare genetic causes of autosomal dominant or recessive hypercholesterolaemia","volume":"62","author":"Soutar","year":"2010","journal-title":"IUBMB Life"},{"key":"2022050522002447100_DDT573C7","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1161\/01.ATV.15.10.1719","article-title":"Differences in the phenotypic characteristics of subjects with familial defective apolipoprotein B-100 and familial hypercholesterolemia","volume":"15","author":"Miserez","year":"1995","journal-title":"Arterioscler. Thromb. Vasc. 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