Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia.
Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia.
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DOI：
10.1056/nejmoa1002926
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发表时间：
2010-12-02
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影响因子：
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通讯作者：
Kathiresan S
中科院分区：
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作者：
Musunuru K;Pirruccello JP;Do R;Peloso GM;Guiducci C;Sougnez C;Garimella KV;Fisher S;Abreu J;Barry AJ;Fennell T;Banks E;Ambrogio L;Cibulskis K;Kernytsky A;Gonzalez E;Rudzicz N;Engert JC;DePristo MA;Daly MJ;Cohen JC;Hobbs HH;Altshuler D;Schonfeld G;Gabriel SB;Yue P;Kathiresan S
我们对患有混合性低脂血症的两个家族成员的基因组所有蛋白质编码区(外显子组)进行了测序，这些成员的特点是血浆低密度脂蛋白胆固醇(LDL)胆固醇、高密度脂蛋白胆固醇(HDL)胆固醇和甘油三酯水平极低。这两名参与者是Angptl3(编码血管生成素样3蛋白)两个不同无义突变的复合杂合子。据报道，Angptl3可以抑制脂蛋白脂肪酶和内皮脂肪酶，从而提高啮齿动物的血浆甘油三酯和高密度脂蛋白胆固醇水平。我们对Angptl3突变的发现突显了该基因在人类低密度脂蛋白胆固醇代谢中的作用，并表明外显子组测序对于识别遗传性疾病的新遗传原因是有用的。(由国家人类基因组研究所和其他机构资助。)
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. (Funded by the National Human Genome Research Institute and others.)