Novel and recurrent mutations of the LDL receptor gene in Korean patients with familial hypercholesterolemia.
We have identified 16 different mutations of the low-density lipoprotein receptor (LDLR) gene in 25 unrelated Korean patients with heterozygous familial hypercholesterolemia (FH), including five novel mutations, C83Y, 661del17, 1705insCTAG, C675X, and 941-1G>A. The 1705insCTAG mutation in which the four 3 cent -terminal nucleotides of exon 11 are duplicated was found to prevent splicing of exon 11 and would therefore generate a truncated polypeptide. The in-frame 36-bp deletion (1591del36) in exon 11, which had been reported only in one Korean FH patient, was also found. We showed that this change affects transport of the LDL receptor from the endoplasmic reticulum to the cell surface. In addition, we found 8 mutations (-136C>T, E119K, E207K, E207X, F382L, R574Q, 1846-1G>A, and P664L) that had been described in other ethnic groups but not in Koreans, and 2 mutations (R94H and D200N) that had been described in Koreans as well as other ethnic groups. 5 mutations (1591del36, E119K, E207X, E207K, and P664L) were found more than once in the Korean FH samples. Identification of the novel and recurring LDLR mutations in Korean FH patients should facilitate prenatal and early diagnosis in families at high risk of FH.
Kim
Ji-Hyun
JH
National Research Laboratory for Cellular Biochemistry, Department of Biochemistry, College of Science, Yonsei University, Seoul 120-749, Korea.
Choi
Ho-Kap
HK
Lee
Haeyul
H
Park
Hyun Young
HY
Kim
Jeong-Ho
JH
Kim
Jong-Won
JW
Kim
Hyon J
HJ
Lee
Seung-Taek
ST
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D016466:CHO Cells; D002648:Child; D006224:Cricetinae; D004252:DNA Mutational Analysis; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D007723:Korea; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism
D011973:Receptors, LDL