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ABCB4突变基因型与表型的相关性

翁宇航 杨永峰

翁宇航, 杨永峰. ABCB4突变基因型与表型的相关性[J]. 临床肝胆病杂志, 2021, 37(11): 2723-2727. DOI: 10.3969/j.issn.1001-5256.2021.11.052
引用本文: 翁宇航, 杨永峰. ABCB4突变基因型与表型的相关性[J]. 临床肝胆病杂志, 2021, 37(11): 2723-2727. DOI: 10.3969/j.issn.1001-5256.2021.11.052
WENG YH, YANG YF. Association between genotype and phenotype of ABCB4 gene mutation[J]. J Clin Hepatol, 2021, 37(11): 2723-2727. DOI: 10.3969/j.issn.1001-5256.2021.11.052
Citation: WENG YH, YANG YF. Association between genotype and phenotype of ABCB4 gene mutation[J]. J Clin Hepatol, 2021, 37(11): 2723-2727. DOI: 10.3969/j.issn.1001-5256.2021.11.052

ABCB4突变基因型与表型的相关性

DOI: 10.3969/j.issn.1001-5256.2021.11.052
基金项目: 

国家自然科学基金 81970454

详细信息
    通讯作者:

    杨永峰,yyf1997@163.com

  • 中图分类号: R575

Association between genotype and phenotype of ABCB4 gene mutation

Research funding: 

National Natural Science Foundation of China 81970454

  • 摘要: ABCB4相关疾病是由于基因突变引起胆汁分泌障碍的综合征,在临床上可以导致胆管损伤、门静脉高压和肝硬化等。近年来随着遗传学和基因测序技术的发展,越来越多的突变位点被人们所发现,然而考虑到该病较为复杂,突变的致病性和致病机制目前尚不明确;而且该病为罕见病,仅通过基础研究或临床资料单方面往往难以确定ABCB4突变致病性,因此亟需建立起ABCB4基因型与表型之间的相关性,在基础研究与临床实践中构建完善体系。

     

  • 表  1  ABCB4突变功能分类及治疗

    项目 严重缺陷 成熟障碍 活性降低 稳定性降低 意义未明
    突变
    (举例)
    无义突变
    移码突变
    缺失突变
    c.1621A>T(p.I541F)
    c.1667T>G(p.L556R)
    c.2564A>T(p.Q855L)
    c.1037G>T(p.S346l)
    c.1069T>C(p.F357L)
    c. 1605G>A(p.G535D)
    c.2177C>T(p.P726L)
    c.2324C>T(p.T775M)
    c.2860G>A(p.G954S)
    c.3228 A>T (p.S1076C)
    c.1270A>G(p.T424A)
    c.1529A>G (p.N510S)
    c.1954A>G(p.R652G)
    c.523A>G(p.T175A)
    潜在治疗
    (与UDCA联用)
    伴侣蛋白(例如环孢菌素A) CFTR增强剂(例如依伐卡托),核受体激动剂(例如贝特类药物),他汀类 核受体激动剂(例如贝特类药物),他汀类药物
    下载: 导出CSV

    表  2  ABCB4相关疾病临床表型及突变

    项目 ICP DILI LPAC PFIC3
    起病时期 妊娠后期 用药相关 40岁以下 婴儿期晚期(30%)至成年期早期
    突变类型 杂合 杂合 杂合 复合杂合,纯合
    突变位点
    (举例)
    c.1529 A>G(p.N510S)
    c.711A>T(p.I237I)
    c.1954A>G(p.R652G)
    c.2290A>C(p.I764L)
    c.3245T>A(p.L1082Q)
    c.523A>G(p.T175A)
    c.1954A>G(p.R652G)
    c.3203T>A(p.V1068G)
    c.140G>A(p.A47G)
    c.1376A>G(p.D459G)
    c.1769G>A (p.R590Q)
    c.1621A>T(p.I541F)
    c.1667T>G(p.L556R)
    c.1270A>G(p.T424A)
    c.1529A>G(p.N510S)
    下载: 导出CSV
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出版历程
  • 收稿日期:  2021-03-17
  • 修回日期:  2021-05-10
  • 网络出版日期:  2021-11-16
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