TABLE 5.

Genetic diagnosis of familial hypercholesterolemia in Korea.

Case numbers	Age	Male	Diagnosis criteria	Genotyping	Main Findings	References
28	NM	NM	(1) Plasma cholesterol levels > 300 mg/dl in adults and > 250 mg/dl in children, (2) a positive family history of hypercholesterolemia, Achilles tendon xanthomas, and coronary artery disease.	Southern blot hybridization with probes encompassing exons 1–18 of the LDLR gene	Two large deletion mutations of the LDLR gene were identified from three FH patients (10.7%).	Chae et al., 1997
80	NM	NM	(1) Plasma cholesterol levels > 300 mg/dl in adults and > 250 mg/dl in children, (2) a positive family history of hypercholesterolemia, Achilles tendon xanthomas, and coronary artery disease.	DNA sequencing for small structural rearrangements of LDLR gene	Three small deletions in exon 11 (FH 2, FH 34, and FH 400) were identified from three unrelated FH families.	Chae et al., 1999
45	NM	NM	LDL-C > 2.6 g/L, a positive family history of hypercholesterolemia or early coronary artery disease, and Achilles tendon xanthomas	Long-distance PCR for LDLR gene	Two large deletion mutations (FH6 and FH 32) were identified in four families	Kim et al., 1999
20	NM	NM	(1) Plasma cholesterol levels > 300 mg/dL in adults and > 250 mg/d: in children, (2) a positive history of hypercholesterolemia or early coronary artery disease, and Achilles tendon xanthomas.	DNA sequencing for LDLR gene by single-strand conformation	LDLR mutations were identified in 5 patients (25.0%).	Shin et al., 2000
489	NM	NM	244 members from 15 normal and 28 FH pedigrees 245 individuals, including 187 normal and 58 FH	Restriction fragment length polymorphisms	Among the 512 possible combinations for the nine polymorphic sites, there were 39 unique haplotypes detected. The four most common haplotypes accounted for 59.4% of those sampled. The haplotypes indicated marked linkage disequilibrium for these 10 sites and throughout the region containing the LDLR gene.	Chae et al., 2001
31	NM	NM	Total cholesterol >290 mg/dL (age > 40) or >220 mg/dL (age < 40), with tendon xanthoma and/or coronary heart disease, or with first-degree relatives who had hypercholesterolemia.	DNA sequencing for LDLR gene by single-strand conformation and by heteroduplex formation	Sixteen different mutations of the LDLR gene were identified in 25 unrelated Korean patients with HeFH (80.6%).	Kim et al., 2004
69	54	29 (42.0%)	Simon Broome criteria	Whole-exome sequencing	Genetic mutations were detected in 23 patients (33.3%).	Han et al., 2015
97	NM	NM	Unrelated patients older than 19 years who had (1) LDL-C > 190 mg/dL without lipid lowering agents and tendon xanthoma or (2) the same LDL-C levels and a family history of coronary artery disease or hypercholesterolemia	Whole exome sequencing, targeted exome sequencing, and Sanger sequencing	Putative pathogenic mutations in LDLR, APOB, or PCSK9 genes were identified in 31 patients (32%).	Shin et al., 2015
97	54.1	38 (39.2%)	Unrelated patients older than 19 years who had (1) LDL-C > 190 mg/dL without lipid lowering agents and tendon xanthoma or (2) the same LDL-C levels and a family history of coronary artery disease or hypercholesterolemia	SNP	Mutation-negative FH patients had higher SNP scores than controls. SNP score analysis could be used for identification of polygenic cause of FH in Korean patients	Kwon et al., 2015
283	63.4	47 (16.6%)	Total cholesterol levels ≥ 290 mg/dL (7.5 mmol/L)	NGS	Seventeen different mutations in LDLR, APOB, and PCSK9 genes were identified by NGS in 23 patients (8.1%). For the 110 subjects with a total cholesterol ≥ 310 mg/dL, 10 variants were identified in 10 patients (9.1%)	Kim et al., 2018

APOB, apolipoprotein B; DNA, deoxyribonucleic acid; FH, familial hypercholesterolemia; LDL-C, low-density lipoprotein cholesterol; LDLR, low-density lipoprotein receptor; NGS, next generation sequencing; NM, not mention; PCR, polymerase chain reaction; PCSK9, proprotein convertase subtilisin/kexin type 9; SNP, single nucleotide polymorphism.