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Familial Defective Apolipoprotein B and Familial Hypobetalipoproteinemia in One Family: Two Neutralizing Mutations

2008; American College of Physicians; Volume: 148; Issue: 9 Linguagem: Inglês

10.7326/0003-4819-148-9-200805060-00022

1539-3704

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,

Lipid metabolism and disorders

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. 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