Familial Defective Apolipoprotein B and Familial Hypobetalipoproteinemia in One Family: Two Neutralizing Mutations
Authors: Anouk van der Graaf, Sigrid W. Fouchier, Maud N. Vissers, Joep C. Defesche, Albert Wiegman, Raaj R. Sankatsing, Barbara A. Hutten, Mieke D. Trip, John J.P. Kastelein
Journal: Annals of Internal Medicine (2008)

Letters6 May 2008Familial Defective Apolipoprotein B and Familial Hypobetalipoproteinemia in One Family: Two Neutralizing MutationsAnouk van der Graaf, MD, Sigrid W. Fouchier, PhD, Maud N. Vissers, PhD, Joep C. Defesche, PhD, Albert Wiegman, MD, PhD, Raaj R. Sankatsing, MD, Barbara A. Hutten, PhD, Mieke D. Trip, MD, PhD, and John J.P. Kastelein, MD, PhDAnouk van der Graaf, MDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Sigrid W. Fouchier, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Maud N. Vissers, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Joep C. Defesche, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Albert Wiegman, MD, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Raaj R. Sankatsing, MDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Barbara A. Hutten, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., Mieke D. Trip, MD, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands., and John J.P. Kastelein, MD, PhDFrom Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-9-200805060-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Some hereditary disorders of lipoprotein metabolism can be characterized by hyper- as well as hypocholesterolemia. We describe a family in which 2 counteracting mutations in the apolipoprotein B gene (APOB) were transmitted and resulted in a clinically normolipidemic phenotype.Case Report: A 38-year-old man (index patient [patient II-4 in Figure]) and 2 of his children (patients III-1 and III-3) had elevated levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (apoB) caused by a point mutation (R3500Q) in APOB, underlying familial defective apolipoprotein B (FDB). In contrast, his spouse (patient II-3) and a third child (patient III-4) had substantially ...References1. Fouchier SW, Sankatsing RR, Peter J, Castillo S, Pocovi M, Alonso R, et al. High frequency of APOB gene mutations causing familial hypobetalipoproteinaemia in patients of Dutch and Spanish descent. J Med Genet. 2005;42:23. [PMID: 15805152] CrossrefMedlineGoogle Scholar2. Schonfeld G, Patterson BW, Yablonskiy DA, Tanoli TS, Averna M, Elias N, et al. Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis. J Lipid Res. 2003;44:470-8. [PMID: 12562873] CrossrefMedlineGoogle Scholar3. Tanoli T, Yue P, Yablonskiy D, Schonfeld G. Fatty liver in familial hypobetalipoproteinemia: roles of the APOB defects, intra-abdominal adipose tissue, and insulin sensitivity. J Lipid Res. 2004;45:941-7. [PMID: 14967820] CrossrefMedlineGoogle Scholar4. Sankatsing RR, Fouchier SW, de Haan S, Hutten BA, de Groot E, Kastelein JJ, et al. Hepatic and cardiovascular consequences of familial hypobetalipoproteinemia. Arterioscler Thromb Vasc Biol. 2005;25:1979-84. [PMID: 16002743] CrossrefMedlineGoogle Scholar5. Kastelein JJ, Wedel MK, Baker BF, Su J, Bradley JD, Yu RZ, et al. Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation. 2006;114:1729-35. [PMID: 17030687] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Academic Medical Centre, University of Amsterdam, Amsterdam 1105 AZ, Netherlands.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited BySuccessful Genetic Screening and Creating Awareness of Familial Hypercholesterolemia and Other Heritable Dyslipidemias in the NetherlandsCan one overcome "unhealthy genes"?The complex molecular genetics of familial hypercholesterolaemiaFamilial hypercholesterolaemiaGenotype-guided diagnosis in familial hypercholesterolemiaCardiovascular risk in relation to functionality of sequence variants in the gene coding for the low-density lipoprotein receptor: a study among 29 365 individuals tested for 64 specific low-density lipoprotein-receptor sequence variantsGenetic variation in APOB , PCSK9 , and ANGPTL3 in carriers of pathogenic autosomal dominant hypercholesterolemic mutations with unexpected low LDL-Cl LevelsLiteraturAssessment of Carotid Atherosclerosis in Normocholesterolemic Individuals With Proven Mutations in the Low-Density Lipoprotein Receptor or Apolipoprotein B GenesFunctionality of sequence variants in the genes coding for the low-density lipoprotein receptor and apolipoprotein B in individuals with inherited hypercholesterolemiaTwo Years after Molecular Diagnosis of Familial Hypercholesterolemia: Majority on Cholesterol-Lowering Treatment but a Minority Reaches Treatment GoalHipobetalipoproteinemia familiar: caracterización clínica de una nueva mutación en el gen de la apolipoproteína B 6 May 2008Volume 148, Issue 9Page: 712-714KeywordsApolipoproteinsCholesterolHypercholesterolemiaLipoprotein metabolismLipoproteinsLiverMutationStable coronary artery diseaseVitamins ePublished: 6 May 2008 Issue Published: 6 May 2008 CopyrightCopyright © 2008 by American College of Physicians. 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