首页|期刊导航|中华医学杂志（英文版）|Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C→T mutation of low-density lipoprotein receptor gene
Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C→T mutation of low-density lipoprotein receptor gene
LIN Jie JIANG Zhi-sheng WANG Lu-ya LIU Shu XIA Jun-hui YONG Qiang DU Lan-ping PAN Xiao-dong XUE Hong CHEN Bao-sheng
中华医学杂志（英文版）2008，Vol.121Issue(9)：776-781,6.
中华医学杂志（英文版）2008，Vol.121Issue(9)：776-781,6.
Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C→T mutation of low-density lipoprotein receptor gene
Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C→T mutation of low-density lipoprotein receptor gene
摘要
Abstract
Background Familial hypercholesterolemia (FH), caused by low density lipoprotein (LDL) receptor (LDL-R) gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited molecular data concerning FH are available in China. The present study described the clinical profiles and cell biological defects of a Chinese FH kindred with novel LDL-R gene mutation.Methods The patient's LDL-R gene coding region was sequenced. The patient's lymphocytes were isolated and the LDL-R expression, binding and up-take functions were observed by immunohistochemistry staining and flow cytometry detection. The patient's heart and the major large vessels were detected by vessel ultrasound examination and myocardial perfusion imaging (MPI).Results The patient's LDL-R expression, LDL binding and up-take functions were significantly lower than normal control (39%, 63% and 76% respectively). A novel homozygous 1439 C→T mutation of the LDL-R gene was detected in the patient and his family. ECG showed atypical angina pectoris. Echocardiogram showed stenosis of the coronary artery and calcification of the aortic valve and its root. Blood vessel ultrasound examination showed the thickness of large vessel intima, and the vessel lumen was narrowed by 71%. MPI showed ischemic changes.Conclusions The LDL-R synthesis dysfunction of FH patients leads to arterial stenosis and calcification, which are the major phenotype of the clinical disorder. The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China.关键词
familial hypercholesterolemia/ LDL receptor/ gene mutation/ gene functionKey words
familial hypercholesterolemia/ LDL receptor/ gene mutation/ gene function分类
医药卫生引用本文复制引用
LIN Jie,JIANG Zhi-sheng,WANG Lu-ya,LIU Shu,XIA Jun-hui,YONG Qiang,DU Lan-ping,PAN Xiao-dong,XUE Hong,CHEN Bao-sheng..Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C→T mutation of low-density lipoprotein receptor gene[J].中华医学杂志（英文版）,2008,121(9):776-781,6.基金项目
This study was supported by grants from the National Natural Science Foundation of China (No. 30470722, 30771982,30772356), Beijing Natural Science Foundation (No. 7052021,7062010), and Science and Technology New Star Funds of Beijing Natural Science Foundation (No. 7052021,7062010), and Science and Technology New Star Funds of Beijing (No. 2004B27, 2005A29). （No. 30470722, 30771982,30772356）
