Exome Sequencing, ANGPTL3 Mutations, and Familial Combined Hypolipidemia

被引：547

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

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