J. Lipid Res.
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A more recent version of this article appeared on October 1, 2003

Papers In Press, published online ahead of print July 1, 2003
J. Lipid Res., doi:10.1194/jlr.M200470-JLR200
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Submitted on December 16, 2002
Revised on June 2, 2003
Accepted on June 27, 2003

Identification and characterization of LDL receptor gene mutations in hyperlipidemic Chinese

Jui-Hung Chang, Ju-Pin Pan, Der-Yan Tai, Ai-Chun Huang, Pi-Hung Li, Hui-Ling Ho, Hui-Ling Hsieh, Shiu-Ching Chou, Wen-Lang Lin, Eric Lo, Ching-Yu Chang, Jerming Tseng, Ming-Tsan Su, and Guey-Jen Lee-Chen

Department of Biology, National Taiwan Normal University, Taipei, Taiwan 116

Corresponding Author: t43019{at}cc.ntnu.edu.tw

DNA screening for low-density lipoprotein (LDL) receptor mutations was performed in 170 unrelated hyperlipidemic Chinese and two clinically diagnosed familial hypercholesterolemia (FH) patients. Two deletions (Del e3-5 and Del e6-8), eight point mutations (W-18X, D69N, R94H, E207K, C308Y, I402T, A410T, A696G), and two polymorphisms (A370T and I602V) were identified. Of these mutations, C308Y and Del e6-8 were found in homozygosity, and D69N and C308Y were seen in unrelated patients. The effects of mutations on LDL receptor function were characterized in COS-7 cells. The LDL receptor level and activity were close to those of wild type in A696G transfected cells. A novel intermediate protein and reduction of LDL receptor activity were seen in D69N transfected cells. For R94H, E207K, C308Y, I402T and A410T mutations, only 20~64% of normal receptor activities were seen. Conversely, Del e3-5 and Del e6-8 lead to defective proteins with 0~13% activity. Most of the mutant receptors were localized intracellularly, with a staining pattern resembling that of ER (D69N, R94H, E207K, C308Y and I402T) or endosome/lysosome (A410T and Del e6-8). Molecular analysis of the LDL receptor gene will clearly identify the cause of the patient's hyperlipidemia and allow appropriate early treatment as well as antenatal and family studies.


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T. Ranheim, M. A. Kulseth, K. E. Berge, and T. P. Leren
Model System for Phenotypic Characterization of Sequence Variations in the LDL Receptor Gene
Clin. Chem., August 1, 2006; 52(8): 1469 - 1479.
[Abstract] [Full Text] [PDF]


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