{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:54:47Z","timestamp":1770972887591,"version":"3.50.1"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Familial chylomicronemia syndrome is a rare autosomal recessive disorder of lipoprotein metabolism characterized by the presence of chylomicrons in fasting plasma and an important increase in plasma triglycerides (TG) levels that can exceed 22.58\u00a0mmol\/l. The disease is associated with recurrent episodes of abdominal pain and pancreatitis, eruptive cutaneous xanthomatosis, lipemia retinalis, and hepatosplenomegaly. A consanguineous Syrian family who migrated to Lebanon was referred to our laboratory after perceiving familial chylomicronemia syndrome in two children. The <jats:italic>LPL<\/jats:italic> and <jats:italic>PCSK9<\/jats:italic> genes were sequenced and plasma PCSK9 levels were measured. Sanger sequencing of the <jats:italic>LPL<\/jats:italic> gene revealed the presence of the p.(Val227Phe) pathogenic variant in exon 5 at the homozygous state in the two affected children, and at the heterozygous state in the other recruited family members. Interestingly, PCSK9 levels in homozygous carriers of the p.(Val227Phe) were \u224850% lower than those in heterozygous carriers of the variant (<jats:italic>p<\/jats:italic>-value = 0.13) and ranged between the 5th and the 7.5th percentile of PCSK9 levels in a sample of Lebanese children of approximately the same age group. Moreover, this is the first reported case of individuals carrying simultaneously an <jats:italic>LPL<\/jats:italic> pathogenic variant and <jats:italic>PCSK9<\/jats:italic> variants, the L10 and L11 leucine insertion, which can lower and raise low-density lipoprotein cholesterol (LDL-C) levels respectively. TG levels fluctuated concomitantly between the two children, were especially high following the migration from a country to another, and were reduced under a low-fat diet. This case is crucial to raise public awareness on the risks of consanguineous marriages to decrease the emergence of inherited autosomal recessive diseases. It also highlights the importance of the early diagnosis and management of these diseases to prevent serious complications, such as recurrent pancreatitis in the case of familial hyperchylomicronemia.<\/jats:p>","DOI":"10.3389\/fgene.2022.961028","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T05:53:45Z","timestamp":1660888425000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon"],"prefix":"10.3389","volume":"13","author":[{"given":"Carine","family":"Ayoub","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yara","family":"Azar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina","family":"Maddah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youmna","family":"Ghaleb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandy","family":"Elbitar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yara","family":"Abou-Khalil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selim","family":"Jambart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathilde","family":"Varret","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Boileau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"El Khoury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Abifadel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1136\/jmg.2008.059980","article-title":"A PCSK9 variant and familial combined hyperlipidaemia","volume":"45","author":"Abifadel","year":"2008","journal-title":"J. Med. Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1111\/j.0009-9163.2004.00205.x","article-title":"Identification of the first Lebanese mutation in the LPL gene and description of a rapid detection method","volume":"65","author":"Abifadel","year":"2004","journal-title":"Clin. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1517\/13543776.2010.518615","article-title":"Strategies for proprotein convertase subtilisin kexin 9 modulation: a perspective on recent patents","volume":"20","author":"Abifadel","year":"2010","journal-title":"Expert Opin. Ther. Pat."},{"key":"B4","doi-asserted-by":"publisher","first-page":"E682","DOI":"10.1002\/humu.21002","article-title":"The molecular basis of familial hypercholesterolemia in Lebanon: spectrum of LDLR mutations and role of PCSK9 as a modifier gene","volume":"30","author":"Abifadel","year":"2009","journal-title":"Hum. Mutat."},{"key":"B5","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/ng1161","article-title":"Mutations in PCSK9 cause autosomal dominant hypercholesterolemia","volume":"34","author":"Abifadel","year":"2003","journal-title":"Nat. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.jaci.2012.11.033","article-title":"Combined immunodeficiency: the Middle East experience","volume":"131","author":"Al-Herz","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.cjca.2013.03.004","article-title":"Regional distribution and metabolic effect of PCSK9 insLEU and R46L gene mutations and apoE genotype","volume":"29","author":"Awan","year":"2013","journal-title":"Can. J. Cardiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"564","DOI":"10.3390\/metabo11090564","article-title":"Identification of a variant in APOB gene as a major cause of hypobetalipoproteinemia in Lebanese families","volume":"11","author":"Ayoub","year":"2021","journal-title":"Metabolites"},{"key":"B9","doi-asserted-by":"publisher","first-page":"504","DOI":"10.3390\/metabo12060504","article-title":"Circulating PCSK9 linked to dyslipidemia in Lebanese schoolchildren","volume":"12","author":"Azar","year":"2022","journal-title":"Metabolites"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.phrs.2018.01.025","article-title":"Proprotein Convertase Subtilisin-Kexin type-9 (PCSK9) and triglyceride-rich lipoprotein metabolism: facts and gaps","volume":"130","author":"Baragetti","year":"2018","journal-title":"Pharmacol. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1161\/ATVBAHA.109.186577","article-title":"Chylomicronemia with a mutant GPIHBP1 (Q115P) that cannot bind lipoprotein lipase","volume":"29","author":"Beigneux","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e203","DOI":"10.1161\/ATVBAHA.122.315499","article-title":"Leu22_Leu23 duplication at the signal peptide of PCSK9 promotes intracellular degradation of LDLr and autosomal dominant hypercholesterolemia","volume":"42","author":"Benito-Vicente","year":"2022","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/S0022-2275(20)37605-7","article-title":"Alterations in plasma lipoproteins and apolipoproteins before the age of 40 in heterozygotes for lipoprotein lipase deficiency","volume":"37","author":"Bijvoet","year":"1996","journal-title":"J. Lipid Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1016\/j.jacl.2018.05.013","article-title":"Characterizing familial chylomicronemia syndrome: baseline data of the APPROACH study","volume":"12","author":"Blom","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1684\/abc.2015.1058","article-title":"Familial hypertriglyceridemia: biochemical, clinical and molecular study in a Moroccan family","volume":"73","author":"Bouabdellah","year":"2015","journal-title":"Ann. Biol. Clin."},{"key":"B16","doi-asserted-by":"publisher","first-page":"981","DOI":"10.3390\/nu5030981","article-title":"Hypertriglyceridemia","volume":"5","author":"Brahm","year":"2013","journal-title":"Nutrients"},{"key":"B17","article-title":"Familial lipoprotein lipase deficiency, apo C-II deficiency, and hepatic lipase deficiency","volume-title":"The online metabolic and molecular bases of inherited disease","author":"Brunzell","year":"2019"},{"key":"B18","article-title":"Familial lipoprotein lipase deficiency","volume-title":"GeneReviews\u00ae","author":"Burnett","year":"1993"},{"key":"B19","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.numecd.2017.11.003","article-title":"Molecular analysis of three known and one novel LPL variants in patients with type I hyperlipoproteinemia","volume":"28","author":"Caddeo","year":"2018","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"B20","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/978-1-4615-9474-1_22","article-title":"Apolipoprotein C-II deficiency","volume-title":"Human apolipoprotein mutants: impact on atherosclerosis and longevity NATO ASI series","author":"Catapano","year":"1986"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1016\/j.jacc.2005.01.051","article-title":"A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis","volume":"45","author":"Chen","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.jacl.2014.02.006","article-title":"Genotype-phenotype relationships in patients with type I hyperlipoproteinemia","volume":"8","author":"Chokshi","year":"2014","journal-title":"J. Clin. Lipidol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1136\/jmg.25.10.649","article-title":"A deletion of one nucleotide results in functional deficiency of apolipoprotein CII (apo CII Toronto)","volume":"25","author":"Cox","year":"1988","journal-title":"J. Med. Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.cmet.2010.04.016","article-title":"GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries","volume":"12","author":"Davies","year":"2010","journal-title":"Cell Metab."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4131","DOI":"10.1021\/bi00436a001","article-title":"Structure of the human lipoprotein lipase gene","volume":"28","author":"Deeb","year":"1989","journal-title":"Biochemistry"},{"key":"B26","doi-asserted-by":"publisher","first-page":"429","DOI":"10.7555\/JBR.29.20150052","article-title":"PCSK9 and triglyceride-rich lipoprotein metabolism","volume":"29","author":"Druce","year":"2015","journal-title":"J. Biomed. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1111\/dom.13181","article-title":"Plasma proprotein-convertase-subtilisin\/kexin type 9 (PCSK9) and cardiovascular events in type 2 diabetes","volume":"20","author":"El Khoury","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"B28","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S0022-3476(98)70280-X","article-title":"Familial lipoprotein lipase deficiency in infancy: clinical, biochemical, and molecular study","volume":"133","author":"Feoli-Fonseca","year":"1998","journal-title":"J. Pediatr."},{"key":"B29","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1111\/j.1365-2796.1992.tb01256.x","article-title":"Hypertriglyceridaemia due to genetic defects in lipoprotein lipase and apolipoprotein C-II","volume":"231","author":"Fojo","year":"1992","journal-title":"J. Intern. Med."},{"key":"B30","first-page":"207","article-title":"Lipoprotein lipase: a multifunctional enzyme in lipoprotein metabolism","volume":"25","author":"Foubert","year":"1996","journal-title":"Presse Med."},{"key":"B31","first-page":"405","article-title":"Primary lipoprotein-lipase-activity deficiency: clinical investigation of a French Canadian population","volume":"140","author":"Gagn\u00e9","year":"1989","journal-title":"CMAJ"},{"key":"B32","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1172\/JCI114732","article-title":"Role of lipoprotein lipase in the regulation of high density lipoprotein apolipoprotein metabolism. Studies in normal and lipoprotein lipase-inhibited monkeys","volume":"86","author":"Goldberg","year":"1990","journal-title":"J. Clin. Invest."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e1082","DOI":"10.1161\/CIR.0000000000000625","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA guideline on the management of blood cholesterol: a report of the American college of cardiology\/American heart association task force on clinical practice guidelines","volume":"139","author":"Grundy","year":"2019","journal-title":"Circulation"},{"key":"B34","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.jacl.2018.03.093","article-title":"Clinical and biochemical features of different molecular etiologies of familial chylomicronemia","volume":"12","author":"Hegele","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"B35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-383834-6.00100-2","article-title":"Chapter 96 - lipoprotein and lipid metabolism","volume-title":"Emery and rimoin\u2019s principles and practice of medical genetics","author":"Hegele","year":"2013"},{"key":"B36","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1136\/jmg.29.2.119","article-title":"The lipoprotein lipase gly188----glu mutation in South Africans of Indian descent: evidence suggesting common origins and an increased frequency","volume":"29","author":"Henderson","year":"1992","journal-title":"J. Med. Genet."},{"key":"B37","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1016\/s0022-2275(20)32382-8","article-title":"Two novel mutations in the lipoprotein lipase gene in a family with marked hypertriglyceridemia in heterozygous carriers. Potential interaction with the polymorphic marker D1S104 on chromosome 1q21-q23","volume":"41","author":"H\u00f6lzl","year":"2000","journal-title":"J. Lipid Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1007\/s00431-004-1474-1","article-title":"Severe hypertriglyceridaemia in a Greek infant: a clinical, biochemical and genetic study","volume":"163","author":"Kavazarakis","year":"2004","journal-title":"Eur. J. Pediatr."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1210\/jc.2009-0141","article-title":"Genetic and metabolic determinants of plasma PCSK9 levels","volume":"94","author":"Lakoski","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B40","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1073\/pnas.86.3.948","article-title":"A major insertion accounts for a significant proportion of mutations underlying human lipoprotein lipase deficiency","volume":"86","author":"Langlois","year":"1989","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B41","doi-asserted-by":"publisher","first-page":"131","DOI":"10.5551\/jat.11.131","article-title":"Mutations in Japanese subjects with primary hyperlipidemia--results from the research committee of the ministry of health and welfare of Japan since 1996--","volume":"11","author":"Maruyama","year":"2004","journal-title":"J. Atheroscler. Thromb."},{"key":"B42","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1172\/JCI116222","article-title":"Heterozygous lipoprotein lipase deficiency due to a missense mutation as the cause of impaired triglyceride tolerance with multiple lipoprotein abnormalities","volume":"91","author":"Miesenb\u00f6ck","year":"1993","journal-title":"J. Clin. Invest."},{"key":"B43","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1093\/cvr\/cvw194","article-title":"Biology of proprotein convertase subtilisin kexin 9: beyond low-density lipoprotein cholesterol lowering","volume":"112","author":"Norata","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.1210\/js.2019-00214","article-title":"Differentiating familial chylomicronemia syndrome from multifactorial severe hypertriglyceridemia by clinical profiles","volume":"3","author":"O\u2019Dea","year":"2019","journal-title":"J. Endocr. Soc."},{"key":"B45","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1017\/S0021932009003411","article-title":"Prevalence of consanguineous marriages in Syria","volume":"41","author":"Othman","year":"2009","journal-title":"J. Biosoc. Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1161\/01.ATV.0000054194.78240.45","article-title":"Apolipoprotein A5, a newly identified gene that affects plasma triglyceride levels in humans and mice","volume":"23","author":"Pennacchio","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1038\/ng.2007.24","article-title":"Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia","volume":"39","author":"P\u00e9terfy","year":"2007","journal-title":"Nat. Genet."},{"key":"B48","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/j.bbalip.2011.10.006","article-title":"Lipase maturation factor 1: A lipase chaperone involved in lipid metabolism","volume":"1821","author":"P\u00e9terfy","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B49","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1016\/j.jacl.2016.02.015","article-title":"Identification and characterization of two novel mutations in the LPL gene causing type I hyperlipoproteinemia","volume":"10","author":"Pingitore","year":"2016","journal-title":"J. Clin. Lipidol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.numecd.2011.04.003","article-title":"Leucine 10 allelic variant in signal peptide of PCSK9 increases the LDL cholesterol-lowering effect of statins in patients with familial hypercholesterolaemia","volume":"22","author":"Pisciotta","year":"2012","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1161\/01.ATV.0000153087.36428.dd","article-title":"Inherited apolipoprotein A-V deficiency in severe hypertriglyceridemia","volume":"25","author":"Priore Oliva","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.ymgme.2007.10.007","article-title":"Monogenic pediatric dyslipidemias: classification, genetics and clinical spectrum","volume":"93","author":"Rahalkar","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"B53","unstructured":"Familial hyperchylomicronemia syndrome\n            RegmiM.\n            RehmanA.\n          2021"},{"key":"B54","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/ng0595-28","article-title":"A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis","volume":"10","author":"Reymer","year":"1995","journal-title":"Nat. Genet."},{"key":"B55","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.jacl.2015.12.015","article-title":"Pathogenic classification of LPL gene variants reported to be associated with LPL deficiency","volume":"10","author":"Rodrigues","year":"2016","journal-title":"J. Clin. Lipidol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e010932","DOI":"10.1161\/JAHA.118.010932","article-title":"Relationship between low-density lipoprotein cholesterol and lipoprotein(a) lowering in response to PCSK9 inhibition with evolocumab","volume":"8","author":"Shapiro","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"B57","doi-asserted-by":"publisher","first-page":"e157500","DOI":"10.1172\/JCI157500","article-title":"Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells","volume":"132","author":"Song","year":"2022","journal-title":"J. Clin. Invest."},{"key":"B58","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s13256-020-02609-0","article-title":"Familial chylomicronemia syndrome: a case report","volume":"15","author":"Susheela","year":"2021","journal-title":"J. Med. Case Rep."},{"key":"B59","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.atherosclerosis.2014.12.017","article-title":"On the function and homeostasis of PCSK9: reciprocal interaction with LDLR and additional lipid effects","volume":"238","author":"Tavori","year":"2015","journal-title":"Atherosclerosis"},{"key":"B60","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.tcm.2019.05.007","article-title":"The PCSK9 revolution: current status, controversies, and future directions","volume":"30","author":"Warden","year":"2020","journal-title":"Trends cardiovasc. Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1172\/JCI114770","article-title":"Phenotypic expression of heterozygous lipoprotein lipase deficiency in the extended pedigree of a proband homozygous for a missense mutation","volume":"86","author":"Wilson","year":"1990","journal-title":"J. Clin. Invest."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1126\/science.3823907","article-title":"Human lipoprotein lipase complementary DNA sequence","volume":"235","author":"Wion","year":"1987","journal-title":"Science"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1172\/JCI119323","article-title":"A common substitution (Asn291Ser) in lipoprotein lipase is associated with increased risk of ischemic heart disease","volume":"99","author":"Wittrup","year":"1997","journal-title":"J. Clin. Invest."},{"key":"B64","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1002\/humu.20316","article-title":"The c.43_44insCTG variation in PCSK9 is associated with low plasma LDL-cholesterol in a Caucasian population","volume":"27","author":"Yue","year":"2006","journal-title":"Hum. Mutat."},{"key":"B65","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/0009-8981(94)90176-7","article-title":"A new case of apo C-II deficiency with a nonsense mutation in the apo C-II gene","volume":"224","author":"Zanelli","year":"1994","journal-title":"Clin. Chim. Acta."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.961028\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T05:53:51Z","timestamp":1660888431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.961028\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,19]]},"references-count":65,"alternative-id":["10.3389\/fgene.2022.961028"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.961028","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,19]]},"article-number":"961028"}}