Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with the APOE p.Leu167del Mutation

被引：96

作者：

Marduel, Marie ^{[1
,2
,3
]}

Ouguerram, Khadija ^{[4
]}

Serre, Valerie ^{[2
,5
]}

Bonnefont-Rousselot, Dominique ^{[3
,6
,7
]}

Marques-Pinheiro, Alice ^{[2
]}

Berge, Knut Erik ^{[8
]}

Devillers, Martine ^{[2
]}

Luc, Gerald ^{[9
,10
]}

Lecerf, Jean-Michel ^{[10
]}

Tosolini, Laurent ^{[1
]}

Erlich, Daniele ^{[5
]}

Peloso, Gina M. ^{[11
]}

Stitziel, Nathan ^{[11
]}

Nitchke, Patrick ^{[3
,12
]}

Jais, Jean-Philippe ^{[3
,12
]}

Abifadel, Marianne ^{[1
,13
]}

Kathiresan, Sekar ^{[11
]}

Leren, Trond Paul ^{[8
]}

Rabes, Jean-Pierre ^{[1
,14
,15
]}

Boileau, Catherine ^{[1
,14
,15
]}

Varret, Mathilde ^{[1
,5
]}

机构：

[1] INSERM, U698, Paris, France

[2] INSERM, U781, Paris, France

[3] Univ Paris 05, Paris, France

[4] Univ Nantes, INSERM, Inst Thorax, U915, Nantes, France

[5] Univ Paris Denis Diderot, Paris, France

[6] Fac Pharm, EA 4466, Paris, France

[7] CHU Pitie Salpetriere, AP HP, Serv Biochim Metab, Paris, France

[8] Univ Oslo, Rikshosp, Oslo Univ Hosp, Med Genet Lab, N-0027 Oslo, Norway

[9] Univ Lille Nord France, Fac Pharm, Lille, France

[10] Univ Hosp Lille, Dept Internal Med, Lille, France

[11] Broad Inst, Cambridge, MA USA

[12] CHU Necker, AP HP, Serv Biostat & Informat Med, Paris, France

[13] Univ St Joseph, Fac Pharm, Beirut, Lebanon

[14] Hop Ambroise Pare, AP HP, Lab Biochim & Genet Mol, Boulogne, France

[15] Univ Versailles St Quentin En Yvelines, UFR Med Paris Ile France Ouest, Guyancourt, France

来源：

HUMAN MUTATION | 2013年 / 34卷 / 01期

关键词：

apolipoprotein E; APOE; hypercholesterolemia; ADH; LDL; SEA-BLUE HISTIOCYTOSIS; RECEPTOR-BINDING ACTIVITY; NIEMANN-PICK-DISEASE; APOLIPOPROTEIN-E; COMBINED HYPERLIPIDEMIA; CLINICAL-DIAGNOSIS; STORAGE DISEASE; GENE-MUTATIONS; LOW-DENSITY; HYPERLIPOPROTEINEMIA;

D O I：

10.1002/humu.22215

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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. Hum Mutat 34:83-87, 2013. (C) 2012 Wiley Periodicals, Inc.

引用

页码：83 / 87

页数：5

共 50 条

[1] APOE p.Leu167del mutation in familial hypercholesterolemia
Awan, Zuhier
Choi, Hong Y.
Stitziel, Nathan
Ruel, Isabelle
Bamimore, Mary Aderayo
Husa, Regina
Gagnon, Marie-Helene
Wang, Rui-Hao L.
Peloso, Gina M.
Hegele, Robert A.
Seidah, Nabil G.
Kathiresan, Sekar
Genest, Jacques
ATHEROSCLEROSIS, 2013, 231 (02) : 218 - 222
[2] APOE P.LEU167DEL MUTATION IN FAMILIAL HYPERCHOLESTEROLEMIA
Awan, Z.
Choi, H. Y.
Stitziel, N.
Ruel, I.
Husa, R.
Gagnon, M.
Wang, R. L.
Seidah, N. G.
Kathiresan, S.
Genest, J.
CANADIAN JOURNAL OF CARDIOLOGY, 2013, 29 (10) : S379 - S380
[3] The p.Leu167del Mutation in APOE Gene Causes Autosomal Dominant Hypercholesterolemia by Down-regulation of LDL Receptor Expression in Hepatocytes
Cenarro, Ana
Etxebarria, Aitor
de Castro-Oros, Isabel
Stef, Marianne
Bea, Ana M.
Palacios, Lourdes
Mateo-Gallego, Rocio
Benito-Vicente, Asier
Ostolaza, Helena
Tejedor, Teresa
Martin, Cesar
Civeira, Fernando
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2016, 101 (05): : 2113 - 2121
[4] The p.Leu167del Mutation in APOE Gene causes Autosomal Dominant Hypercholesterolemia by Down-Regulation of LDL Receptor Expression in Hepatocytes
Cenarro, Ana
Martin, Cesar
Stef, Marianne
de Castro-Ords, Isabel
Etxebarria, Aitor
Palacios, Lourdes
Mateo-Gallego, Rocio
Ostolaza, Helena
Tejedor, Teresa
Civeira, Fernando
CIRCULATION, 2014, 130
[5] IDENTIFICATION OF P.LEU167DEL APOE GENE MUTATION BY NEXT GENERATION SEQUENCING IN A LARGE HYPERCHOLESTEROLEMIC FAMILY
Scrimali, C.
Spina, R.
Ingrassia, V.
Cefalu, A. B.
Brucato, F.
Misiano, G.
Valenti, V.
Noto, D.
Altieri, G. I.
Fayer, F.
Giammanco, A.
Barbagallo, C.
Averna, M.
ATHEROSCLEROSIS, 2019, 287 : E213 - E213
[6] The First Japanese Case of Familial Hypercholesterolemia Caused by an APOE p.Leu167del Mutation: A Case Report
Tada, Hayato
Nomura, Akihiro
Kawashiri, Masa-aki
Takamura, Masayuki
INTERNAL MEDICINE, 2024,
[7] Inherited lipemic splenomegaly and the spectrum of apolipoprotein E p.Leu167del mutation phenotypic variation
Okorodudu, Daniel E.
Crowley, Matthew J.
Sebastian, Siby
Rowell, Jennifer V.
Guyton, John R.
JOURNAL OF CLINICAL LIPIDOLOGY, 2013, 7 (06) : 566 - 572
[8] LIPID-LOWERING RESPONSE IN SUBJECTS WITH THE P.(LEU167DEL) MUTATION IN APOE GENE
Bea, A. M.
Lamiquiz-Moneo, I.
Marco-Benedi, V.
Mateo-Gallego, R.
Perez-Calahorra, S.
Jarauta, E.
Martin, C.
Cenarro, A.
Civeira, F.
ATHEROSCLEROSIS, 2019, 287 : E109 - E109
[9] Lipid-lowering response in subjects with the p.(Leu167del) mutation in the APOE gene
Bea, Ana M.
Lamiquiz-Moneo, Itziar
Marco-Benedi, Victoria
Mateo-Gallego, Rocio
Perez-Calahorra, Sofia
Jarauta, Estibaliz
Martin, Cesar
Cenarro, Ana
Civeira, Fernando
ATHEROSCLEROSIS, 2019, 282 : 143 - 147
[10] Ocular signs associated with a rhodopsin mutation (Cys-167→Arg) in a family with autosomal dominant retinitis pigmentosa
Simonelli, F
Rinaldi, M
Nesti, A
Testa, F
Rinaldi, E
Ciccodicola, A
Flagiello, L
Miano, MG
Ventruto, V
D'Urso, M
BRITISH JOURNAL OF OPHTHALMOLOGY, 1998, 82 (06) : 709 - 709

← 1 2 3 4 5 →