Identification of four novel mutations of the low-density lipoprotein receptor gene in Korean patients with familial hypercholesterolemia

• Published in: Clinical genetics 2000-03, Vol.57 (3), p.225-229
• Main Authors: Shin, Jin A, Han Kim, Sung, Kyung Kim, Un, Jin Chae, Jae, Joon Choe, Seong, Namkoong, Yong, Soo Kim, Hyo, Bae Park, Young, Choo Lee, Chung
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Disorders of blood lipids. Hyperlipoproteinemia; DNA Mutational Analysis; Exons; familial hypercholesterolemia; Family Health; Female; Humans; Hyperlipoproteinemia Type II - genetics; Korea; low-density lipoprotein receptor gene; Male; Medical sciences; Metabolic diseases; Middle Aged; Mutation; Mutation, Missense; Point Mutation; Polymorphism, Single-Stranded Conformational; Receptors, LDL - genetics; single-strand conformation polymorphism; Tropical medicine
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1034/j.1399-0004.2000.570309.x

To obtain insight into the genetic variation of the low‐density lipoprotein (LDL) receptor gene in Korean patients with familial hypercholesterolemia (FH), we used single‐strand conformation polymorphism to screen all 18 exons and a promotor of the LDL receptor gene in 20 unrelated Korean FH patients. Four novel point mutations were detected in 5 FH patients and were characterized by sequence analysis. Of them, one is a nonsense mutation, a Glu→Stop (C AG→T AG) at codon 161, and results in a large deletion. The other three, which were a Ala→Glu (GC G→GĀG) mutation at signal peptide, Cys→Tyr (TG C→TĀC) at codon 210, and Pro→Leu (CT G→CC G) at codon 584, were novel missense mutations, which modified the highly conserved region of the LDL receptor gene. All these mutations were absent in normolipidemic controls and were associated in heterozygote carriers with clinical signs of FH. Identification of these novel mutations provides another example of the molecular heterogeneity of the LDL receptor gene mutations causing FH.