一个家族性高胆固醇血症家系的基因突变筛查与评估

doi:10.3969/j.issn.1004-616x.2020.03.013

癌变·畸变·突变 ›› 2020, Vol. 32 ›› Issue (3): 229-232,245.doi: 10.3969/j.issn.1004-616x.2020.03.013

一个家族性高胆固醇血症家系的基因突变筛查与评估

张佳虹¹, 张庆英¹, 张燕虹¹, 陈甲连¹, 谢芳², 刘锐国¹, 吴容¹, 吴龙飞¹

1. 汕头大学医学院公共卫生与预防医学教研室, 广东汕头 515041;
2. 云南省玉溪市红塔区疾病预防控制中心慢性病防治科, 云南玉溪 653100

收稿日期:2020-02-15 修回日期:2020-04-30 出版日期:2020-05-31 发布日期:2020-06-03
通讯作者: 张庆英,E-mail:qyzhang@stu.edu.cn E-mail:qyzhang@stu.edu.cn
作者简介:张佳虹,E-mail:1141498278@qq.com。

Screening and evaluation of gene mutations in a familial hypercholesterolemia family

ZHANG Jiahong¹, ZHANG Qingying¹, ZHANG Yanhong¹, CHEN Jialian¹, XIE Fang², LIU Ruiguo¹, WU Rong¹, WU Longfei¹

1. Department of Public Health and Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong;
2. Hongta District Center for Disease Control and Prevention, Yuxi 653100, Yunnan, China

Received:2020-02-15 Revised:2020-04-30 Online:2020-05-31 Published:2020-06-03

摘要/Abstract

摘要： 目的：对一个临床诊断的家族性高胆固醇血症（FH）家系进行全基因组外显子测序，以寻找该家系的致病基因。方法：采集该家系成员外周静脉血样本，检测血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）这四项指标，并提取白细胞DNA进行全基因组外显子测序，筛选出4个FH相关基因LDLR、APOB、PCSK9、LDLRAP1的单核苷酸多态性（SNP）位点情况并进行生物信息学分析，采用Polyphen-2和SIFT软件对SNP位点进行致病性分析。结果：该家系APOB基因的SNP位点rs676210、rs679899、c.10094A > T和c.9937C > G均可能与血脂增高有关，但这些位点均不与疾病表型共分离。经Polyphen-2和SIFT软件预测未发现LDLR，PCSK9和LDLRAP1基因的致病性变异。结论：该FH家系存在可能与血脂增高相关的APOB基因SNP位点，其功能尚需进一步的实验验证。

关键词: 家族性高胆固醇血症, 基因突变, APOB基因, 血脂

Abstract: OBJECTIVE: To find pathogenic gene(s) in a clinically diagnosed familial hypercholesterolemia (FH) family using whole exome sequencing. METHODS: Peripheral venous blood of the family members was taken to measure serum TC,TG,LDL cholesterol and HDL cholesterol. DNA of the white blood cell was extracted to perform whole exome sequencing. Four genes (LDLR,APOB,PCSK9,LDLRAP1) associated with FH were chosen to analyze single nucleotide polymorphisms (SNP) and predict the function of protein using Polyphen-2 and SIFT. RESULTS: Four SNPs (rs676210,rs679899,c.10094A > T and c.9937C > G) of APOB might be associated with the elevated lipid levels,but no co-segregating variants were found in this family. No damaging variant was found in LDLR,PCSK9 and LDLRAP1 by Polyphen-2 and SIFT. CONCLUSION: Our study found that some SNPs of APOB may be associated with elevated lipid levels in a clinically diagnosed FH family. The function of these SNPs still needs further experiments to confirm.

Key words: familial hypercholesterolemia, gene mutations, APOB gene, blood lipids

中图分类号:

R124

张佳虹, 张庆英, 张燕虹, 陈甲连, 谢芳, 刘锐国, 吴容, 吴龙飞. 一个家族性高胆固醇血症家系的基因突变筛查与评估[J]. 癌变·畸变·突变, 2020, 32(3): 229-232,245.

ZHANG Jiahong, ZHANG Qingying, ZHANG Yanhong, CHEN Jialian, XIE Fang, LIU Ruiguo, WU Rong, WU Longfei. Screening and evaluation of gene mutations in a familial hypercholesterolemia family[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(3): 229-232,245.

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一个家族性高胆固醇血症家系的基因突变筛查与评估

Screening and evaluation of gene mutations in a familial hypercholesterolemia family

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