Identification and characterization of a novel 43-bp deletion mutation of the ATP7B gene in a Chinese patient with Wilson's disease: a case report.
Identification and characterization of a novel 43-bp deletion mutation of the ATP7B gene in a Chinese patient with Wilson's disease: a case report.
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中国威尔逊氏病患者 ATP7B 基因的新型 43 bp 缺失突变的鉴定和表征：病例报告
DOI：
10.1186/s12881-018-0567-z
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发表时间：
2018-04-12
影响因子：
--
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Liu G;Ma D;Cheng J;Zhang J;Luo C;Sun Y;Hu P;Wang Y;Jiang T;Xu Z
威尔逊病（WD）是一种常染色体隐性遗传疾病，其特征是铜蓄积。ATP 7 B基因突变导致ATP 7 B蛋白功能障碍，进而导致Wilson病。我们描述了一个男性威尔逊氏病诊断后10年的常规生化测试，显示低血清铜蓝蛋白水平和凯泽-弗莱舍环在两个角膜。ATP 7 B基因的分析揭示了先证者的复合杂合突变，包括报道的c.3517G > A突变和新的c.532_574del突变。c.532_574del突变覆盖外显子2的43-bp区域，并导致移码突变（p.Leu178PhefsX10）。通过碱基序列分析，在ATP 7 B基因的两个缺失断点上观察到两个微同源性（TCTCA）。同时，在缺失区附近存在一些与DNA断裂相关的序列基序，促进了DNA链断裂。通过比较，一个基于复制的机制命名为叉失速和模板转换/微同源介导的断裂诱导复制（FoSTeS/MMBIR）被用来解释这种新的缺失突变的形成。本文的在线版本（10.1186/s12881-018-0567-z）包含补充材料，可供授权用户使用。
Wilson’s disease (WD) is an autosomal recessive disorder characterized by copper accumulation. ATP7B gene mutations lead to ATP7B protein dysfunction, which in turn causes Wilson’s disease. We describe a male case of Wilson’s disease diagnosed at 10 years after routine biochemical test that showed low serum ceruloplasmin levels and Kayser–Fleischer rings in both corneas. Analysis of the ATP7B gene revealed compound heterozygous mutations in the proband, including the reported c.3517G > A mutation and a novel c.532_574del mutation. The c.532_574del mutation covered a 43-bp region in exon 2, and resulted in a frameshift mutation (p.Leu178PhefsX10). By base sequence analysis, two microhomologies (TCTCA) were observed on both deletion breakpoints in the ATP7B gene. Meanwhile, the presence of some sequence motifs associated with DNA breakage near the deletion region promoted DNA strand break. By comparison, a replication-based mechanism named fork stalling and template switching/ microhomology-mediated break-induced replication (FoSTeS/MMBIR) was used to explain the formation of this novel deletion mutation. The online version of this article (10.1186/s12881-018-0567-z) contains supplementary material, which is available to authorized users.
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影响因子：
4.5
作者：
Yousefzadeh MJ;Wyatt DW;Takata K;Mu Y;Hensley SC;Tomida J;Bylund GO;Doublié S;Johansson E;Ramsden DA;McBride KM;Wood RD
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影响因子：
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作者：
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DOI：
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发表时间：
2008-11
期刊：
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影响因子：
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通讯作者：
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