Title: Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with the<i>APOE</i>p.Leu167del Mutation
Abstract: Human MutationVolume 34, Issue 1 p. 83-87 Brief Report Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with the APOE p.Leu167del Mutation Marie Marduel, Marie Marduel INSERM U698, Paris, France INSERM U781, Paris, France Université Paris Descartes, Paris, FranceSearch for more papers by this authorKhadija Ouguerram, Khadija Ouguerram INSERM U915, Institut du Thorax, Université de Nantes, Nantes, FranceSearch for more papers by this authorValérie Serre, Valérie Serre INSERM U781, Paris, France Université Paris Denis Diderot, Paris, FranceSearch for more papers by this authorDominique Bonnefont-Rousselot, Dominique Bonnefont-Rousselot Université Paris Descartes, Paris, France EA 4466, Faculté de Pharmacie, Paris, France AP-HP, CHU Pitié-Salpêtrière, Service de Biochimie Métabolique, Paris, FranceSearch for more papers by this authorAlice Marques-Pinheiro, Alice Marques-Pinheiro INSERM U781, Paris, FranceSearch for more papers by this authorKnut Erik Berge, Knut Erik Berge Medical Genetics Laboratory, Oslo University Hospital Rikshospitalet, Oslo, NorwaySearch for more papers by this authorMartine Devillers, Martine Devillers INSERM U781, Paris, FranceSearch for more papers by this authorGérald Luc, Gérald Luc Faculté de Pharmacie, Université de Lille—Nord de France, Lille, France Department of Internal Medicine, University Hospital of Lille, Lille, FranceSearch for more papers by this authorJean-Michel Lecerf, Jean-Michel Lecerf Department of Internal Medicine, University Hospital of Lille, Lille, FranceSearch for more papers by this authorLaurent Tosolini, Laurent Tosolini INSERM U698, Paris, FranceSearch for more papers by this authorDanièle Erlich, Danièle Erlich Université Paris Denis Diderot, Paris, FranceSearch for more papers by this authorGina M. Peloso, Gina M. Peloso Broad Institute, Cambridge, MassachusettsSearch for more papers by this authorNathan Stitziel, Nathan Stitziel Broad Institute, Cambridge, MassachusettsSearch for more papers by this authorPatrick Nitchké, Patrick Nitchké Université Paris Descartes, Paris, France Service de Biostatistique et Informatique Médicale, AP-HP, CHU Necker, Paris, FranceSearch for more papers by this authorJean-Philippe Jaïs, Jean-Philippe Jaïs Université Paris Descartes, Paris, France Service de Biostatistique et Informatique Médicale, AP-HP, CHU Necker, Paris, FranceSearch for more papers by this authorThe French Research Network on ADH, The French Research Network on ADH The French Research Network on ADH: Dr. Bernard Chanu (Bondy), Pr. Jacques Bonnet (Bordeaux), Pr. Yves Reznik (Caen), Dr. Michel Farnier (Dijon), Pr. Philippe Moulin, Dr. Laurence Perrot (Lyon), Pr. Michel Krempf, Dr. Yassine Zaïr (Nantes), Pr. Alexandre Fredenrich (Nice), Dr. Alain Carrié, Dr. Phillipe Giral, Dr. Athina Kalopissis, Pr. Eric Bruckert, Pr. Jean-Philippe Girardet, Pr. Michel Polak (Paris), Pr. Vincent Durlach (Reims), Pr. Jean-Louis Schlienger (Strasbourg), Pr. Jean Ferrières, Dr. Dorotha Ferrières, Dr. Vanina Bongard, and Dr. Maxime Cournot (Toulouse).Search for more papers by this authorMarianne Abifadel, Marianne Abifadel INSERM U698, Paris, France Faculté de Pharmacie, Université St-Joseph, Beirut, LebanonSearch for more papers by this authorSekar Kathiresan, Sekar Kathiresan Broad Institute, Cambridge, MassachusettsSearch for more papers by this authorTrond Paul Leren, Trond Paul Leren Medical Genetics Laboratory, Oslo University Hospital Rikshospitalet, Oslo, NorwaySearch for more papers by this authorJean-Pierre Rabès, Jean-Pierre Rabès INSERM U698, Paris, France AP-HP, Hôpital Ambroise Paré, Laboratoire de Biochimie et Génétique Moléculaire, Boulogne-Billancourt, France Université Versailles Saint-Quentin-en-Yvelines, UFR de Médecine Paris Ile-de-France Ouest, Guyancourt, FranceSearch for more papers by this authorCatherine Boileau, Catherine Boileau INSERM U698, Paris, France AP-HP, Hôpital Ambroise Paré, Laboratoire de Biochimie et Génétique Moléculaire, Boulogne-Billancourt, France Université Versailles Saint-Quentin-en-Yvelines, UFR de Médecine Paris Ile-de-France Ouest, Guyancourt, FranceSearch for more papers by this authorMathilde Varret, Corresponding Author Mathilde Varret INSERM U698, Paris, France Université Paris Denis Diderot, Paris, France Correspondence to: Mathilde Varret, INSERM U698, CHU Xavier Bichat Secteur Claude Bernard, 46 rue Henri Huchard, 75018 Paris, France. E-mail: [email protected] for more papers by this author Marie Marduel, Marie Marduel INSERM U698, Paris, France INSERM U781, Paris, France Université Paris Descartes, Paris, FranceSearch for more papers by this authorKhadija Ouguerram, Khadija Ouguerram INSERM U915, Institut du Thorax, Université de Nantes, Nantes, FranceSearch for more papers by this authorValérie Serre, Valérie Serre INSERM U781, Paris, France Université Paris Denis Diderot, Paris, FranceSearch for more papers by this authorDominique Bonnefont-Rousselot, Dominique Bonnefont-Rousselot Université Paris Descartes, Paris, France EA 4466, Faculté de Pharmacie, Paris, France AP-HP, CHU Pitié-Salpêtrière, Service de Biochimie Métabolique, Paris, FranceSearch for more papers by this authorAlice Marques-Pinheiro, Alice Marques-Pinheiro INSERM U781, Paris, FranceSearch for more papers by this authorKnut Erik Berge, Knut Erik Berge Medical Genetics Laboratory, Oslo University Hospital Rikshospitalet, Oslo, NorwaySearch for more papers by this authorMartine Devillers, Martine Devillers INSERM U781, Paris, FranceSearch for more papers by this authorGérald Luc, Gérald Luc Faculté de Pharmacie, Université de Lille—Nord de France, Lille, France Department of Internal Medicine, University Hospital of Lille, Lille, FranceSearch for more papers by this authorJean-Michel Lecerf, Jean-Michel Lecerf Department of Internal Medicine, University Hospital of Lille, Lille, FranceSearch for more papers by this authorLaurent Tosolini, Laurent Tosolini INSERM U698, Paris, FranceSearch for more papers by this authorDanièle Erlich, Danièle Erlich Université Paris Denis Diderot, Paris, FranceSearch for more papers by this authorGina M. Peloso, Gina M. Peloso Broad Institute, Cambridge, MassachusettsSearch for more papers by this authorNathan Stitziel, Nathan Stitziel Broad Institute, Cambridge, MassachusettsSearch for more papers by this authorPatrick Nitchké, Patrick Nitchké Université Paris Descartes, Paris, France Service de Biostatistique et Informatique Médicale, AP-HP, CHU Necker, Paris, FranceSearch for more papers by this authorJean-Philippe Jaïs, Jean-Philippe Jaïs Université Paris Descartes, Paris, France Service de Biostatistique et Informatique Médicale, AP-HP, CHU Necker, Paris, FranceSearch for more papers by this authorThe French Research Network on ADH, The French Research Network on ADH The French Research Network on ADH: Dr. Bernard Chanu (Bondy), Pr. Jacques Bonnet (Bordeaux), Pr. Yves Reznik (Caen), Dr. Michel Farnier (Dijon), Pr. Philippe Moulin, Dr. Laurence Perrot (Lyon), Pr. Michel Krempf, Dr. Yassine Zaïr (Nantes), Pr. Alexandre Fredenrich (Nice), Dr. Alain Carrié, Dr. Phillipe Giral, Dr. Athina Kalopissis, Pr. Eric Bruckert, Pr. Jean-Philippe Girardet, Pr. Michel Polak (Paris), Pr. Vincent Durlach (Reims), Pr. Jean-Louis Schlienger (Strasbourg), Pr. Jean Ferrières, Dr. Dorotha Ferrières, Dr. Vanina Bongard, and Dr. Maxime Cournot (Toulouse).Search for more papers by this authorMarianne Abifadel, Marianne Abifadel INSERM U698, Paris, France Faculté de Pharmacie, Université St-Joseph, Beirut, LebanonSearch for more papers by this authorSekar Kathiresan, Sekar Kathiresan Broad Institute, Cambridge, MassachusettsSearch for more papers by this authorTrond Paul Leren, Trond Paul Leren Medical Genetics Laboratory, Oslo University Hospital Rikshospitalet, Oslo, NorwaySearch for more papers by this authorJean-Pierre Rabès, Jean-Pierre Rabès INSERM U698, Paris, France AP-HP, Hôpital Ambroise Paré, Laboratoire de Biochimie et Génétique Moléculaire, Boulogne-Billancourt, France Université Versailles Saint-Quentin-en-Yvelines, UFR de Médecine Paris Ile-de-France Ouest, Guyancourt, FranceSearch for more papers by this authorCatherine Boileau, Catherine Boileau INSERM U698, Paris, France AP-HP, Hôpital Ambroise Paré, Laboratoire de Biochimie et Génétique Moléculaire, Boulogne-Billancourt, France Université Versailles Saint-Quentin-en-Yvelines, UFR de Médecine Paris Ile-de-France Ouest, Guyancourt, FranceSearch for more papers by this authorMathilde Varret, Corresponding Author Mathilde Varret INSERM U698, Paris, France Université Paris Denis Diderot, Paris, France Correspondence to: Mathilde Varret, INSERM U698, CHU Xavier Bichat Secteur Claude Bernard, 46 rue Henri Huchard, 75018 Paris, France. E-mail: [email protected] for more papers by this author First published: 04 September 2012 https://doi.org/10.1002/humu.22215Citations: 88 Communicated by Hans R. Waterham Contract grant sponsors: NIH (R01HL107816); GIS-Maladies Rares; PHRC (AOM06024) and ANR (ANR-05-PCOD-017, ANR-06-MRAR-038, and ANR-08-GENO-002–01); Ministère de l'Education Nationale et de la Technologie (France); Région Ile de France and Conseil de la Recherche de l'Université Saint-Joseph (Beirut, Lebanon). Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat ABSTRACT Apolipoprotein (apo) E mutants are associated with type III hyperlipoproteinemia characterized by high cholesterol and triglycerides levels. Autosomal dominant hypercholesterolemia (ADH), due to the mutations in the LDLR, APOB, or PCSK9 genes, is characterized by an isolated elevation of cholesterol due to the high levels of low-density lipoproteins (LDLs). We now report an exceptionally large family including 14 members with ADH. Through genome-wide mapping, analysis of regional/functional candidate genes, and whole exome sequencing, we identified a mutation in the APOE gene, c.500_502delTCC/p.Leu167del, previously reported associated with sea-blue histiocytosis and familial combined hyperlipidemia. We confirmed the involvement of the APOE p.Leu167del in ADH, with (1) a predicted destabilization of an alpha-helix in the binding domain, (2) a decreased apo E level in LDLs, and (3) a decreased catabolism of LDLs. Our results show that mutations in the APOE gene can be associated with bona fide ADH. Citing Literature Supporting Information Disclaimer: Supplementary materials have been peer-reviewed but not copyedited. Filename Description humu22215-sup-0001-FigureS1.pdf333.3 KB Supplementary Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume34, Issue1January 2013Pages 83-87 RelatedInformation