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N Engl J Med DOI:10.1056/NEJMoa1002926

Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia.

Publication TypeJournal Article
Year of Publication2010
AuthorsMusunuru, 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
JournalN Engl J Med
Volume363
Issue23
Pages2220-7
Date Published2010 Dec 2
ISSN1533-4406
KeywordsAngiopoietins, Cholesterol, HDL, Cholesterol, LDL, Codon, Nonsense, DNA Mutational Analysis, Female, Genetic Linkage, Humans, Hypobetalipoproteinemias, Male, Pedigree
Abstract

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.).

DOI10.1056/NEJMoa1002926
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/20942659?dopt=Abstract

Alternate JournalN. Engl. J. Med.
PubMed ID20942659
PubMed Central IDPMC3008575
Grant ListK99 HL098364 / HL / NHLBI NIH HHS / United States
K99 HL098364 / HL / NHLBI NIH HHS / United States
K99 HL098364-02 / HL / NHLBI NIH HHS / United States
R01 HL082896 / HL / NHLBI NIH HHS / United States
R01 HL082896 / HL / NHLBI NIH HHS / United States
R01 HL082896-05 / HL / NHLBI NIH HHS / United States
RC1 HL099634 / HL / NHLBI NIH HHS / United States
RC1 HL099634 / HL / NHLBI NIH HHS / United States
RC1 HL099634-02 / HL / NHLBI NIH HHS / United States
RC1 HL099793 / HL / NHLBI NIH HHS / United States
RC1 HL099793 / HL / NHLBI NIH HHS / United States
RC1 HL099793-02 / HL / NHLBI NIH HHS / United States
RC2 HL101864 / HL / NHLBI NIH HHS / United States
RC2 HL101864 / HL / NHLBI NIH HHS / United States
RC2 HL101864-02 / HL / NHLBI NIH HHS / United States
RL1 HL092550 / HL / NHLBI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U54 HG003067-06 / HG / NHGRI NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada