Exome Sequencing,ANGPTL3Mutations, and Familial Combined Hypolipidemia

• DOI: 10.1056/nejmoa1002926
• Publication Date: 2010-10-13T19:06:02Z
• Authors: Kiran Musunuru; James P. Pirruccello; Ron Do; Gina M. Peloso; Candace Guiducci; Carrie Sougnez; Kiran V. Garimella; Sheila Fisher; Justin Abreu; Andrew J. Barry; Tim Fennell; Eric Banks; Lauren Ambrogio; Kristian Cibulskis; Andrew Kernytsky; Elena Gonzalez; Nicholas Rudzicz; James C. Engert; Mark A. DePristo; Mark J. Daly; Jonathan C. Cohen; Helen H. Hobbs; David Altshuler; Gustav Schonfeld; Stacey B. Gabriel; Pin Yue; Sekar Kathiresan
• Keywords: Exome; Nonsense mutation

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