Exome Sequencing, ANGPTL3 Mutations, and Familial Combined Hypolipidemia

被引：539

作者：

Musunuru, Kiran ^{[1
,2
,4
,7
,8
]}

Pirruccello, James P. ^{[1
,2
,7
,8
]}

Do, Ron ^{[1
,2
,7
,9
]}

Peloso, Gina M. ^{[6
,10
]}

Guiducci, Candace ^{[7
]}

Sougnez, Carrie ^{[7
]}

Garimella, Kiran V. ^{[7
]}

Fisher, Sheila ^{[7
]}

Abreu, Justin ^{[7
]}

Barry, Andrew J. ^{[7
]}

Fennell, Tim ^{[7
]}

Banks, Eric ^{[7
]}

Ambrogio, Lauren ^{[7
]}

Cibulskis, Kristian ^{[7
]}

Kernytsky, Andrew ^{[7
]}

Gonzalez, Elena ^{[7
]}

Rudzicz, Nicholas ^{[9
]}

Engert, James C. ^{[9
]}

DePristo, Mark A. ^{[7
]}

Daly, Mark J. ^{[1
,4
,7
]}

Cohen, Jonathan C. ^{[11
,12
]}

Hobbs, Helen H. ^{[11
,12
]}

Altshuler, David ^{[1
,3
,4
,5
,7
]}

Schonfeld, Gustav ^{[13
]}

Gabriel, Stacey B. ^{[7
]}

Yue, Pin ^{[13
]}

Kathiresan, Sekar ^{[1
,2
,4
,7
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA

[5] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA

[6] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[7] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[8] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

[9] McGill Univ, Dept Human Genet, Montreal, PQ, Canada

[10] NHLBI, Framingham Heart Study, Framingham, MA USA

[11] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA

[12] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA

[13] Washington Univ, Sch Med, St Louis, MO USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2010年 / 363卷 / 23期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

LOW-DENSITY-LIPOPROTEIN; APO-B GENE; APOLIPOPROTEIN-B; FATTY LIVER; CAUCASIAN FAMILIES; HYPOBETALIPOPROTEINEMIA; METABOLISM; LIPASE; INHIBITION; CAPTURE;

D O I：

10.1056/NEJMoa1002926

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We sequenced all protein-coding regions of the genome (the "exome") in two family members with combined hypolipidemia, marked by extremely low plasma levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. These two participants were compound heterozygotes for two distinct nonsense mutations in ANGPTL3 (encoding the angiopoietin-like 3 protein). ANGPTL3 has been reported to inhibit lipoprotein lipase and endothelial lipase, thereby increasing plasma triglyceride and HDL cholesterol levels in rodents. Our finding of ANGPTL3 mutations highlights a role for the gene in LDL cholesterol metabolism in humans and shows the usefulness of exome sequencing for identification of novel genetic causes of inherited disorders.

引用

页码：2220 / 2227

页数：8

共 23 条

[1] A decreased expression of angiopoietin-like 3 is protective against atherosclerosis in apoE-deficient mice
Ando, Y
Shimizugawa, T
Takeshita, S
Ono, M
Shimamura, M
Koishi, R
Furukawa, H
[J]. JOURNAL OF LIPID RESEARCH, 2003, 44 (06) : 1216 - 1223
[2] Genetic diagnosis by whole exome capture and massively parallel DNA sequencing
Choi, Murim
Scholl, Ute I.
Ji, Weizhen
Liu, Tiewen
Tikhonova, Irina R.
Zumbo, Paul
Nayir, Ahmet
Bakkaloglu, Aysin
Ozen, Seza
Sanjad, Sami
Nelson-Williams, Carol
Farhi, Anita
Mane, Shrikant
Lifton, Richard P.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (45) : 19096 - 19101
[3] In vivo metabolism of ApoB, ApoA-I, and VLDL triglycerides in a form of hypobetalipoproteinemia not linked to the ApoB gene
Elias, N
Patterson, BW
Schonfeld, G
[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2000, 20 (05) : 1309 - 1315
[4] Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing
Gnirke, Andreas
Melnikov, Alexandre
Maguire, Jared
Rogov, Peter
LeProust, Emily M.
Brockman, William
Fennell, Timothy
Giannoukos, Georgia
Fisher, Sheila
Russ, Carsten
Gabriel, Stacey
Jaffe, David B.
Lander, Eric S.
Nusbaum, Chad
[J]. NATURE BIOTECHNOLOGY, 2009, 27 (02) : 182 - 189
[5] Monogenic hypocholesterolaemic lipid disorders and apolipoprotein B metabolism
Hooper, AJ
van Bockxmeer, FM
Burnett, JR
[J]. CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES, 2005, 42 (5-6) : 515 - 545
[6] Hepatic proprotein convertases modulate HDL metabolism
Jin, Weijun
Wang, Xun
Millar, John S.
Quertermous, Thomas
Rothblat, George H.
Glick, Jane M.
Rader, Daniel J.
[J]. CELL METABOLISM, 2007, 6 (02) : 129 - 136
[7] Angptl3 regulates lipid metabolism in mice
Koishi, R
Ando, Y
Ono, M
Shimamura, M
Yasumo, H
Fujiwara, T
Horikoshi, H
Furukawa, H
[J]. NATURE GENETICS, 2002, 30 (02) : 151 - 157
[8] Transgenic angiopoietin-like (Angptl)4 overexpression and targeted disruption of Angptl4 and Angptl3:: Regulation of triglyceride metabolism
Köster, A
Chao, YB
Mosior, M
Ford, A
Gonzalez-De Whitt, PA
Hale, JE
Li, DS
Qiu, YB
Fraser, CC
Yang, DD
Heuer, JG
Jaskunas, SR
Eacho, P
[J]. ENDOCRINOLOGY, 2005, 146 (11) : 4943 - 4950
[9] Identification of a New Functional Domain in Angiopoietin-like 3 (ANGPTL3) and Angiopoietin-like 4 (ANGPTL4) Involved in Binding and Inhibition of Lipoprotein Lipase (LPL)
Lee, E-Chiang
Desai, Urvi
Gololobov, Gennady
Hong, Seokjoo
Feng, Xiao
Yu, Xuan-Chuan
Gay, Jason
Wilganowski, Nat
Gao, Cuihua
Du, Ling-Ling
Chen, Joan
Hu, Yi
Zhao, Sharon
Kirkpatrick, Laura
Schneider, Matthias
Zambrowicz, Brian P.
Landes, Greg
Powell, David R.
Sonnenburg, William K.
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (20) : 13735 - 13745
[10] Exome sequencing identifies the cause of a mendelian disorder
Ng, Sarah B.
Buckingham, Kati J.
Lee, Choli
Bigham, Abigail W.
Tabor, Holly K.
Dent, Karin M.
Huff, Chad D.
Shannon, Paul T.
Jabs, Ethylin Wang
Nickerson, Deborah A.
Shendure, Jay
Bamshad, Michael J.
[J]. NATURE GENETICS, 2010, 42 (01) : 30 - U41

← 1 2 3 →