LAUSR

BACKGROUND We found a large family with familial hypercholesterolemia (FH) that included 7 siblings who all developed myocardial infarction. OBJECTIVE The aim of this study was to identify the pathogenic gene underlying FH in the family. METHODS Whole-genome sequencing (WGS) was performed in 12 affected and 10 unaffected individuals in the family. RESULTS WGS identified a novel large duplication: copy number variation (CNV) in the LDLR gene, exon2_6dup (c.68-499_940+252dup), that was present in the 12 affected family members but not in any of the 10 unaffected family members. The exact extent and genomic breakpoint sequence of the duplication caused by nonallelic homologous recombination between Alu sequences were identified based on bioinformatic analysis of WGS data for the LDLR gene. CONCLUSIONS A novel c.68-499_940+252dup variant in the LDLR gene was identified based on bioinformatic analysis of WGS data. WGS is a powerful tool that can be used to precisely identify CNVs in addition to small-scale variations in FH-related genes.