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《Journal of Applied Clinical Pediatrics》 2009-01
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Detection of W462X Mutation in Low Density Lipoprotein Receptor Gene of A Familial Hypercholesterolemia Patient and Its Clinical Significance

LIU Shu,WANG Lu-ya,LIN Jie,YONG Qiang,YANG Ya,WU Bang-jun,PAN Xiao-dong,DU Lan-ping,QIN Yan-wen(Department of Atherosclerosis,Beijing Institute of Heart Lung and Blood Vessel Diseases,Beijing Anzhen Hospital Affiliated to Capital University of Medical Sciences,Beijing 100029,China)  
Objective To explore the molecular basis of familial hypercholesteraemia(FH)by analyzing the phenotype and genotype relationship through identify the low density liporotein receptor(LDL-r)gene mutation in a FH kindred.Methods A male patient of 15 years old was selected to examine the electrocardiogram,lipid.Color Doppler was used to examine heart and great vessels.The promoter region and the 18 exons of the LDL-r gene were screened by touch-down polymerase chain reaction(PCR)and DNA sequencing.Results The caro-tid intima-media thickness(IMT)was increased to 0.23 cm,while coronary flow velocity reserve(CFVR)was decreased to 1.57,and mode-rate mitral regurgitation was found in the proband.The genetic alteration G→A change at 1 448 of exon 10 causing premature stop codon(W462X).The same heterozygous nonsense mutation was also found in his father.The mutation had been reported in other Chinese patients.In vitro experiments showed that W462X mutation leads to low LDL binding and internalization ability.Conclusions The homozygous mutation(W462X)in exon 10 of the LDL-r gene were identified in the clinically heterozygous FH proband.The W462X mutation is the underl-ying cause of hypercholesterolaemia and clinical AS manifestations.W462X is recurrent mutation among Chinese FH patients.It might be a hot spot mutation in LDL-r in Chinese FH.J Appl Clin Pediatr,2009,24(1):18-20
【Fund】: 国家自然科学基金项目资助(30470722 30771986);; 北京市自然科学基金项目资助(7032012 7042023 7052021 7062010);; 北京市科技新星项目资助(04B29 05A29)
【CateGory Index】: R725.8
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