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

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 exon s and a promotor of the LDL receptor gene in 20 unrelated Korean FH patient s. Four novel point mutations were detected in 5 FH patients and were chara cterized by sequence analysis. Of them, one is a nonsense mutation, a Glu - -> Stop (CAG --> TAG) at codon 161, and results in a large deletion. The ot her three, which were a Ala --> Glu (GCG --> GAG) mutation at signal peptid e, Cys --> Tyr (TGC --> TAC) at codon 210, and Pro --> Leu (CTG --> CCG) at codon 584, were novel missense mutations, which modified the highly conser ved region of the LDL receptor gene. All these mutations were absent in nor molipidemic controls and were associated in heterozygote carriers with clin ical signs of FH. Identification of these novel mutations provides another example of the molecular heterogeneity of the LDL receptor gene mutations c ausing FH.