title: Genetic testing of Korean familial hypercholesterolemia using whole-exome sequencing.
abstract: Familial hypercholesterolemia (FH) is a genetic disorder with an increased risk of early-onset 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 PCSK9 were 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.
authors.affiliation: Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Soo Min
authors.initials: SM
authors.lastname: Han
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, Korea.
authors.forename: Byungjin
authors.initials: B
authors.lastname: Hwang
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, Korea.
authors.forename: Tae-gun
authors.initials: TG
authors.lastname: Park
authors.affiliation: Cardiology Division, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Do-Il
authors.initials: DI
authors.lastname: Kim
authors.affiliation: Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, Korea.
authors.forename: Moo-Yong
authors.initials: MY
authors.lastname: Rhee
authors.affiliation: Cardiology Division, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Byoung-Kwon
authors.initials: BK
authors.lastname: Lee
authors.affiliation: Heart Center of Chonnam National University Hospital, Gwangju, Korea.
authors.forename: Young Keun
authors.initials: YK
authors.lastname: Ahn
authors.affiliation: Cardiology Division, Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University College of Medicine, Chunchon, Korea.
authors.forename: Byung Ryul
authors.initials: BR
authors.lastname: Cho
authors.affiliation: Endocrinology Division, Department of Internal Medicine, Kyunghee University School of Medicine, Seoul, Korea.
authors.forename: Jeongtaek
authors.initials: J
authors.lastname: Woo
authors.affiliation: Cardiology Division, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, Korea.
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Hur
authors.affiliation: Cardiology Division, Department of Internal Medicine, School of Medicine, Chungnam National University, Chungnam National University Hospital, Daejeon, Korea.
authors.forename: Jin-Ok
authors.initials: JO
authors.lastname: Jeong
authors.affiliation: Cardiology Division, Department of Internal Medicine, Severance Cardiovascular Hospital, Seoul, Korea; Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea.
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.affiliation: Cardiology Division, Department of Internal Medicine, Severance Cardiovascular Hospital, Seoul, Korea; Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea.
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.affiliation: Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, Korea.
authors.forename: Duhee
authors.initials: D
authors.lastname: Bang
authors.affiliation: Department of Oral Biology, College of Dentistry, Yonsei University, Seoul, Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Cardiology Division, Department of Internal Medicine, Severance Cardiovascular Hospital, Seoul, Korea; Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea.
authors.forename: Sang-Hak
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000235:genetics; D044466:Asian People; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D006937:Hypercholesterolemia / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D001055:Apolipoproteins B; C573412:LDLR protein, human; D011973:Receptors, LDL; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases