Analysis of low-density lipoprotein receptor gene mutations in a Chinese patient with clinically homozygous familial hypercholesterolemia

作     者：曹守春 王绿娅 秦彦文 蔺洁 吴邦俊 刘舒 潘晓冬 杜兰平 陈保生 

作者机构：Laboratory of Infection and ImmunityCapital Institute of Pediatrics Institute of Heart Lung and Blood Vessel Diseases State Key Laboratory of Medical Molecular BiologyBasic Medical Institute Chinese Academy of Medical Sciences 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2003年第116卷第10期

页      面：1535-1538页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 07[理学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 071007[理学-遗传学] 10[医学] 

基　　金：ThisstudywassupportedbygrantsfromBeijingNaturalScienceFoundation (No .70 3 2 0 12 )andBase ClinicalMedicineCooperationFoundationofCapitalUniversityofMedicalScience (No .0 2JL19) 

主　　题：familial hypercholesterolemia low-density lipoprotein polymerase chain reaction DNA sequencing 

摘      要：Objective To screen the point mutation of the low-density lipoprotein receptor (LDL-R) gene in Chinese familial hypercholesterolemia (FH) patients,characterize the relationship between the genotype and the phenotype and discuss the molecular pathological mechanism of FH. Methods A patient with clinical phenotype of homozygous FH and her parents were investigated for mutations in the promoter and all eighteen exons of the LDL-R gene. Screening was carried out using Touch-down PCR and direct DNA sequencing; multiple alignment analysis by DNASIS 2.5 was used to find base alteration,and the LDL-R gene mutation database was searched to identify the alteration. In addition,the apolipoprotein B gene (apo B) was screened for known mutations (R3500Q) that cause familial defective apo B 100 (FDB) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results Two new heterozygous mutations in exons 4 and 9 of the LDL-R gene were identified in the proband (C122Y and T383I) as well as her parents. Both of the mutations have not been published in the LDL-R gene mutation database. No mutation of apo B 100 (R3500Q) was observed. Conclusion Two new mutations (C112Y and T383I) were found in the LDL-R gene,which may result in FH and may be particularly pathogenetic genotypes in Chinese people.