title: Targeted next-generation sequencing in monogenic dyslipidemias.
abstract: OBJECTIVE
  To evaluate the potential clinical translation of high-throughput next-generation sequencing (NGS) methods in diagnosis and management of dyslipidemia.
  
  
  RESULTS
  Recent NGS experiments indicate that most causative genes for monogenic dyslipidemias are already known. Thus, monogenic dyslipidemias can now be diagnosed using targeted NGS. Targeting of dyslipidemia genes can be achieved by either: designing custom reagents for a dyslipidemia-specific NGS panel; or performing genome-wide NGS and focusing on genes of interest. Advantages of the former approach are lower cost and limited potential to detect incidental pathogenic variants unrelated to dyslipidemia. However, the latter approach is more flexible because masking criteria can be altered as knowledge advances, with no need for re-design of reagents or follow-up sequencing runs. Also, the cost of genome-wide analysis is decreasing and ethical concerns can likely be mitigated. DNA-based diagnosis is already part of the clinical diagnostic algorithms for familial hypercholesterolemia. Furthermore, DNA-based diagnosis is supplanting traditional biochemical methods to diagnose chylomicronemia caused by deficiency of lipoprotein lipase or its co-factors.
  
  
  CONCLUSIONS
  The increasing availability and decreasing cost of clinical NGS for dyslipidemia means that its potential benefits can now be evaluated on a larger scale.
authors.affiliation: Robarts Research Institute and Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Ban
authors.forename: Henian
authors.initials: H
authors.lastname: Cao
authors.forename: Adam D
authors.initials: AD
authors.lastname: McIntyre
authors.forename: John F
authors.initials: JF
authors.lastname: Robinson
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D050171:Dyslipidemias / Q000175:diagnosis / Q000235:genetics*; D059472:Exome; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D025202:Molecular Diagnostic Techniques; D017422:Sequence Analysis, DNA