Exome Sequencing, ANGPTL3 Mutations, and Familial Combined Hypolipidemia
Broad Institute · Boston University · +10 more institutions
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…
Citation impact
- FWCI
- 30.57
- Percentile
- 100%
- References
- 24
Authors
27- KMKiran MusunuruCorresponding
Broad Institute, Boston University, Harvard University, Johns Hopkins University, Johns Hopkins Medicine, Massachusetts General Hospital, Center for Human Genetics
- JPJames P. Pirruccello
Broad Institute, Johns Hopkins University, Johns Hopkins Medicine, Massachusetts General Hospital, Center for Human Genetics
- RDRon Do
Broad Institute, Massachusetts General Hospital, Center for Human Genetics, McGill University
- GMGina M. Peloso
Boston University, National Heart Lung and Blood Institute, Framingham Heart Study
- CGCandace Guiducci
Broad Institute
Topics & keywords
- Exome sequencing
- Exome
- Genetics
- Nonsense mutation
- Medicine
- Endocrinology
- Lipoprotein lipase
- Cholesterol
Funding
- DFDonovan Family Foundation
- BIBroad Institute
- SCSarnoff Cardiovascular Research Foundation
- NINational Institutes of HealthAwards: U54 HG003067, HG003067
- CICanadian Institutes of Health Research
- NHNational Heart, Lung, and Blood Institute
- NHNational Human Genome Research InstituteAwards: HG003067, U54 HG003067