Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations
Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations
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DOI：
10.1186/1471-2350-12-6
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发表时间：
2011-01-11
影响因子：
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通讯作者：
Zhang, Xin-Xin
中科院分区：
文献类型：
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作者：
Li, Xin-Hua;Lu, Yi;Zhang, Xin-Xin
背景：威尔逊氏病是一种罕见的常染色体隐性遗传病。在这里，我们评估了来自中国汉族人群的62例WND（58个先证），以扩大我们对ATP7B突变的认识，并更完整地表征中国的WND。方法：对62例中国WND患者（男37例，女25例，年龄2例，接近61岁）的ATP7B基因编码区和启动子区进行直接测序分析。结果：神经系统表现与诊断年龄较大（p < 0.0001）和诊断延迟较长（p < 0.0001）相关。诊断年龄也与尿铜浓度相关（r = 0.58, p < 0.001）。在这些患者中发现了40种不同的突变，其中包括14种新的突变。常见突变包括p. Arg778Leu（31.9%）和p. pro992leu（11.2%）。纯合子p. Arg778Leu和无义突变/移码突变更常与原发性肝脏表现（p = 0.0286和p = 0.0383）和诊断时较高的丙氨酸转氨酶水平（p = 0.0361和p = 0.0047）相关。无义突变/移码突变也与血清铜蓝蛋白降低相关（p = 0.0065）。结论：我们鉴定出14个新的ATP7B突变，并发现中国的ATP7B突变谱与西方国家有很大的不同。突变类型对临床表现有预测作用。基因检测是检测幼儿，特别是8岁以下患者的WND的宝贵工具。4个外显子（8、12、13和16）和2个突变（p.Arg778Leu, p.Pro992Leu）应该被认为是中国高成本效益检测的优先选择。
Background: Wilson's disease (WND) is a rare autosomal recessive disorder. Here we have evaluated 62 WND cases (58 probands) from the Chinese Han population to expand our knowledge of ATP7B mutations and to more completely characterize WND in China.Methods: The coding and promoter regions of the ATP7B gene were analyzed by direct sequencing in 62 Chinese patients (58 probands) with WND (male, n = 37; female, n = 25; age range, 2 similar to 61 years old).Results: Neurologic manifestations were associated with older age at diagnosis (p < 0.0001) and longer diagnostic delay (p < 0.0001). Age at diagnosis was also correlated with urinary copper concentration (r = 0.58, p < 0.001). Forty different mutations, including 14 novel mutations, were identified in these patients. Common mutations included p. Arg778Leu (31.9%) and p.Pro992Leu (11.2%). Homozygous p. Arg778Leu and nonsense mutation/frameshift mutations were more often associated with primary hepatic manifestations (p = 0.0286 and p = 0.0383, respectively) and higher alanine transaminase levels at diagnosis (p = 0.0361 and p = 0.0047, respectively). Nonsense mutation/frameshift mutations were also associated with lower serum ceruloplasmin (p = 0.0065).Conclusions: We identified 14 novel mutations and found that the spectrum of mutations of ATP7B in China is quite distinct from that of Western countries. The mutation type plays a role in predicting clinical manifestations. Genetic testing is a valuable tool to detect WND in young children, especially in patients younger than 8 years old. Four exons (8, 12, 13, and 16) and two mutations (p.Arg778Leu, p.Pro992Leu) should be considered high priority for cost-effective testing in China.