[HTML][HTML] Exome Sequencing, ANGPTL3 Mutations, and Familial Combined Hypolipidemia

K Musunuru, JP Pirruccello, R Do… - … England Journal of …, 2010 - Mass Medical Soc
K Musunuru, JP Pirruccello, R Do, GM Peloso, C Guiducci, C Sougnez, KV Garimella
New England Journal of Medicine, 2010Mass Medical Soc
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 …
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.)
The New England Journal Of Medicine