{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:13:46Z","timestamp":1791112426127,"version":"4.1.0"},"reference-count":30,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>Our discovery in 2003 of the first mutations of <jats:italic>PCSK9<\/jats:italic> gene causing autosomal dominant hypercholesterolaemia (ADH) shed light on an unknown factor that strongly influences the level of circulating low density lipoprotein cholesterol (LDL-C). <jats:italic>PCSK9<\/jats:italic> gain of function mutations cause hypercholesterolaemia by a reduction of LDL receptor levels, while <jats:italic>PCSK9<\/jats:italic> loss of function variants are associated with a reduction of LDL-C values and a decreased risk of coronary heart disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results:<\/jats:title>\n                  <jats:p>We report an insertion of two leucines (p.L21tri also designated p.L15_L16ins2L) in the leucine stretch of the signal peptide of <jats:italic>PCSK9<\/jats:italic> that is found in two of 25 families with familial combined hyperlipidaemia (FCHL). This mutant is associated with high total cholesterol and LDL-C values in these families and is found also in a patient with familial hypercholesterolaemia and her father.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>\n                     <jats:italic>PCSK9<\/jats:italic> variants might contribute to FCHL phenotype and are to be taken into consideration in the study of this complex and multigenic disease with other genes implicated in dyslipidaemia.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2008.059980","type":"journal-article","created":{"date-parts":[[2008,8,18]],"date-time":"2008-08-18T19:21:21Z","timestamp":1219087281000},"page":"780-786","source":"Crossref","is-referenced-by-count":44,"title":["A <i>PCSK9<\/i> variant and familial combined hyperlipidaemia"],"prefix":"10.1136","volume":"45","author":[{"given":"M","family":"Abifadel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Bernier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Dubuc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Nuel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J-P","family":"Rab\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Bonneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Marques","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Marduel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Devillers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Munnich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Erlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Varret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Davignon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Boileau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2008,8,15]]},"reference":[{"key":"2025101713285302000_45.12.780.1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1161"},{"key":"2025101713285302000_45.12.780.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0009-9163.2004.0238.x"},{"key":"2025101713285302000_45.12.780.3","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9383"},{"key":"2025101713285302000_45.12.780.4","doi-asserted-by":"publisher","DOI":"10.1086\/500615"},{"key":"2025101713285302000_45.12.780.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa054013"},{"key":"2025101713285302000_45.12.780.6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107332"},{"key":"2025101713285302000_45.12.780.7","first-page":"8","article-title":"Familial 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