Familial hypercholesterolemia (FH) is a genetic disorder with an increased risk of earlyonset coronary artery disease. Although some clinically diagnosed FH cases are caused by mutations in LDLR, APOB, or PCSK9, mutation detection rates and profiles can vary across ethnic groups. In this study, we aimed to provide insight into the spectrum of FH-causing mutations in Koreans. Among 136 patients referred for FH, 69 who met Simon Broome criteria with definite family history were enrolled. By whole-exome sequencing (WES) analysis, we confirmed that the 3 known FH-related genes accounted for genetic causes in 23 patients (33.3%). A substantial portion of the mutations (19 of 23 patients, 82.6%) resulted from 17 mutations and 2 copy number deletions in LDLR gene. Two mutations each in the APOB and PCSK9 genes were verified. Of these anomalies, two frameshift deletions in LDLR and one mutation in PCSK9were identified as novel causative mutations. In particular, one novel mutation and copy number deletion were validated by co-segregation in their relatives. This study confirmed the utility of genetic diagnosis of FH through WES.
Bibliographical noteFunding Information:
Biospecimens and data were provided by the Korean Genome Analysis Project (4845–301), the Korean Genome and Epidemiology Study (4851–302), and the Korea Biobank Project (4851–307, KBP-2013-42), which were in turn supported by the Korea Center for Disease Control. Support was also provided by the Korean Society of Lipidology and Atherosclerosis and the Cardiovascular Research Center. We are grateful to Jiyeong Jeong, RN, for her excellent assistance with clinical data collection and patient care.
© 2015 Han et al.
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