Use of Next-Generation Sequencing to Detect Copy Number Variations in the Molecular Diagnosis of Familial Hypercholesterolemia

Aim: The molecular diagnosis of familial hypercholesterolemia (FH) is trending towards the use of next-generation sequencing (NGS) panels to interrogate canonical FH-associated genes—LDLR, APOB, and PCSK9—for clinically relevant small-scale variants. However, large-scale copy number variants (CNVs) constitute 10-15% of LDLR variants in many cohorts. Because these are not routinely accessible by NGS, multiplex ligation-dependent probe amplification (MLPA) is required to screen for them. To increase efficiency and decrease costs, use of a single platform to detect both small and large-scale variants would be clinically beneficial. Here we determine the accuracy of NGS bioinformatic tools in identifying CNVs.