• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

日本北部家族性高胆固醇血症中低密度脂蛋白受体的八个新突变及功能损伤

Eight novel mutations and functional impairments of the LDL receptor in familial hypercholesterolemia in the north of Japan.

作者信息

Hattori Hiroaki, Hirayama Tsunenori, Nobe Yukiko, Nagano Makoto, Kujiraoka Takeshi, Egashira Tohru, Ishii Jun, Tsuji Masahiro, Emi Mitsuru

机构信息

Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.

出版信息

J Hum Genet. 2002;47(2):80-7. doi: 10.1007/s100380200005.

DOI:10.1007/s100380200005
PMID:11916007
Abstract

In the course of investigations of familial coronary artery disease in Hokkaido, the northland of Japan, we identified 13 families affected by familial hypercholesterolemia. Among them, we identified eight novel mutations of the low-density lipoprotein (LDL) receptor gene, four of which caused frameshifts: (1) a 7-bp deletion at nucleotide (nt) 578-584 (codon 172-174, exon 4); (2) a 14-bp insertion at 682nt (codon 207-208, exon 4); (3) a 49-bp deletion at nt 943-991 (codon 294-310, exon 7); and (4) a one-base insertion of C to a stretch of C3 at nucleotides 1687-1689 or codon 542. The others included (5) a T-to-C transition at nt 1072 causing substitution of Cys for Arg at codon 337 (C337R, exon 8); (6) a splice-site G-to-T substitution in intron 11; (7) a splice-site G-to-C substitution in intron 11; and (8) a G-to-T transition at nt 1731 causing substitution of Trp for Cys at codon 556 (W556C, exon 12). To disclose the functional consequences of novel mutations, we characterized each of these mutations by two assays in peripheral lymphocytes, i.e., uptake of fluorescently labeled LDL by LDL receptors, and measurement of cell surface-bound LDL receptor protein using specific monoclonal antibody against LDL receptor.

摘要

在对日本北部北海道地区的家族性冠状动脉疾病进行调查的过程中，我们鉴定出了13个受家族性高胆固醇血症影响的家族。其中，我们发现了低密度脂蛋白（LDL）受体基因的8种新突变，其中4种导致移码突变：（1）核苷酸（nt）578 - 584（密码子172 - 174，外显子4）处7个碱基对的缺失；（2）682nt（密码子207 - 208，外显子4）处14个碱基对的插入；（3）nt 943 - 991（密码子294 - 310，外显子7）处49个碱基对的缺失；以及（4）在核苷酸1687 - 1689或密码子542处的一段C3中插入一个碱基C。其他突变包括：（5）nt 1072处的T到C转换，导致密码子337处的精氨酸被半胱氨酸取代（C337R，外显子8）；（6）内含子11中剪接位点G到T的替换；（7）内含子11中剪接位点G到C的替换；以及（8）nt 1731处的G到T转换，导致密码子556处的半胱氨酸被色氨酸取代（W556C，外显子12）。为了揭示新突变的功能后果，我们通过在外周血淋巴细胞中的两种检测方法对每个突变进行了表征，即通过LDL受体摄取荧光标记的LDL，以及使用针对LDL受体的特异性单克隆抗体测量细胞表面结合的LDL受体蛋白。

相似文献

1
Eight novel mutations and functional impairments of the LDL receptor in familial hypercholesterolemia in the north of Japan.日本北部家族性高胆固醇血症中低密度脂蛋白受体的八个新突变及功能损伤
J Hum Genet. 2002;47(2):80-7. doi: 10.1007/s100380200005.
2
Five familial hypercholesterolemic kindreds in Japan with novel mutations of the LDL receptor gene.日本五个家族性高胆固醇血症家系中低密度脂蛋白受体基因的新突变
J Hum Genet. 1998;43(4):250-4. doi: 10.1007/s100380050083.
3
Two novel mutations consisting in minor gene rearrangements in the human low density lipoprotein receptor gene in Italian patients affected by familial hypercholesterolemia. Mutations in brief no. 194. Online.在意大利患有家族性高胆固醇血症的患者中，人类低密度脂蛋白受体基因存在两种由微小基因重排构成的新突变。突变简讯第194号。在线发布。
Hum Mutat. 1998;12(3):290.
4
Two novel mutations of the LDL receptor gene associated with familial hypercholesterolemia in a Chinese family.在中国一个家族中发现与家族性高胆固醇血症相关的两种新型低密度脂蛋白受体基因突变。
Chin Med J (Engl). 2007 Oct 5;120(19):1694-9.
5
Six novel mutations of the LDL receptor gene in FH kindred of Sicilian and Paraguayan descent.西西里和巴拉圭血统的家族性高胆固醇血症（FH）患者中低密度脂蛋白受体基因的六个新突变
Int J Mol Med. 2006 Mar;17(3):539-46.
6
A novel LDLR mutation, H190Y, in a Utah kindred with familial hypercholesterolemia.在一个患有家族性高胆固醇血症的犹他州家族中发现一种新的低密度脂蛋白受体（LDLR）突变，H190Y。
J Hum Genet. 1999;44(6):364-7. doi: 10.1007/s100380050179.
7
Identification of two novel LDL receptor gene defects in French-Canadian pediatric population: mutational analysis and biochemical studies.在法裔加拿大儿童群体中鉴定出两种新型低密度脂蛋白受体基因缺陷：突变分析和生化研究。
Hum Mutat. 1997;9(6):555-62. doi: 10.1002/(SICI)1098-1004(1997)9:6<555::AID-HUMU9>3.0.CO;2-0.
8
A novel splice site mutation of the LDL receptor gene in a Tunisian hypercholesterolemic family.突尼斯一个高胆固醇血症家族中低密度脂蛋白受体基因的一种新型剪接位点突变。
Clin Chim Acta. 2008 Jun;392(1-2):25-9. doi: 10.1016/j.cca.2008.02.019. Epub 2008 Mar 4.
9
Two novel mutations 685del 1 and D129G in the low-density lipoprotein receptor gene in a compound heterozygote Chinese family with familial hypercholesterolemia.一个中国家族性高胆固醇血症复合杂合子家系中低密度脂蛋白受体基因的两个新突变685del 1和D129G
Metabolism. 2007 May;56(5):636-40. doi: 10.1016/j.metabol.2006.12.011.
10
Functional analysis of low-density lipoprotein receptor in homozygous familial hypercholesterolemia patients with novel 1439 C-->T mutation of low-density lipoprotein receptor gene.低密度脂蛋白受体基因发生新型1439 C→T突变的纯合子家族性高胆固醇血症患者中低密度脂蛋白受体的功能分析
Chin Med J (Engl). 2008 May 5;121(9):776-81.

引用本文的文献

1
Identification of New Genetic Determinants in Pediatric Patients with Familial Hypercholesterolemia Using a Custom NGS Panel.使用定制 NGS .panel 鉴定家族性高胆固醇血症儿科患者中的新遗传决定因素。
Genes (Basel). 2022 Jun 1;13(6):999. doi: 10.3390/genes13060999.
2
Identification of amino acid residues in the ligand binding repeats of LDL receptor important for PCSK9 binding.鉴定 LDL 受体配体结合重复序列中对 PCSK9 结合重要的氨基酸残基。
J Lipid Res. 2019 Mar;60(3):516-527. doi: 10.1194/jlr.M089193. Epub 2019 Jan 7.
3
Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr Variants.
验证 LDLr 活性作为改善家族性高胆固醇血症遗传诊断的工具：对 LDLr 变异体功能特征的回顾性研究。
Int J Mol Sci. 2018 Jun 5;19(6):1676. doi: 10.3390/ijms19061676.
4
Analysis of publicly available LDLR, APOB, and PCSK9 variants associated with familial hypercholesterolemia: application of ACMG guidelines and implications for familial hypercholesterolemia diagnosis.分析与家族性高胆固醇血症相关的 LDLR、APOB 和 PCSK9 常见变异：ACMG 指南的应用及其对家族性高胆固醇血症诊断的影响。
Genet Med. 2018 Jun;20(6):591-598. doi: 10.1038/gim.2017.151. Epub 2017 Oct 26.
5
The Genetic Spectrum of Familial Hypercholesterolemia (FH) in the Iranian Population.伊朗人群家族性高胆固醇血症（FH）的遗传谱。
Sci Rep. 2017 Dec 6;7(1):17087. doi: 10.1038/s41598-017-17181-9.
6
Association of single nucleotide polymorphisms in the promoter region of the pro-opiomelanocortin gene (POMC) with low bone mineral density in adult women.促黑素细胞激素原基因（POMC）启动子区域单核苷酸多态性与成年女性低骨密度的关联
J Hum Genet. 2005;50(5):235-240. doi: 10.1007/s10038-005-0244-x. Epub 2005 Apr 29.
7
Association of nucleotide variations in the apolipoprotein B48 receptor gene (APOB48R) with hypercholesterolemia.载脂蛋白B48受体基因（APOB48R）核苷酸变异与高胆固醇血症的关联。
J Hum Genet. 2005;50(4):203-209. doi: 10.1007/s10038-005-0240-1. Epub 2005 Apr 14.
8
The important role for betaVLDLs binding at the fourth cysteine of first ligand-binding domain in the low-density lipoprotein receptor.β极低密度脂蛋白在低密度脂蛋白受体第一个配体结合结构域的第四个半胱氨酸处结合的重要作用。
J Hum Genet. 2004;49(11):622-628. doi: 10.1007/s10038-004-0198-4. Epub 2004 Oct 1.
9
Functional impairment of two novel mutations detected in lipoprotein-associated phospholipase A2 (Lp-PLA2) deficiency patients.脂蛋白相关磷脂酶A2（Lp-PLA2）缺乏症患者中检测到的两种新突变的功能损害。
J Hum Genet. 2004;49(6):302-307. doi: 10.1007/s10038-004-0151-6. Epub 2004 May 18.
10
Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: intrafamilial association study in an eight-generation hyperlipidemic kindred.可溶性环氧化物水解酶变体（Glu287Arg）改变家族性高胆固醇血症患者的血浆总胆固醇和甘油三酯表型：一项对一个八代高脂血症家族的家族内关联研究。
J Hum Genet. 2004;49(1):29-34. doi: 10.1007/s10038-003-0103-6. Epub 2003 Dec 13.