High prevalence of the H1069Q mutation in East German patients with Wilson disease:: rapid detection of mutations by limited sequencing and phenotype-genotype analysis
High prevalence of the H1069Q mutation in East German patients with Wilson disease:: rapid detection of mutations by limited sequencing and phenotype-genotype analysis
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DOI：
10.1016/s0168-8278(01)00219-7
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发表时间：
2001-11-01
影响因子：
25.7
通讯作者：
Berr, F
中科院分区：
文献类型：
--
作者：
Caca, K;Ferenci, P;Berr, F
背景/目的：威尔逊病是由 ATP7B 基因中大量不同的突变引起的。研究了来自同质种族背景 (Saxonia) 的威尔逊病患者 ATP7B 突变的分布和表型。方法：对 82 名患者进行了分析。通过基于聚合酶链式反应的限制性片段长度多态性测试来测定H1069Q突变。对全部外显子 8 和 15 以及 30 个非 H1069Q 纯合子中的整个基因进行了测序。结果：发现了 4 个新突变和 12 个已知突变。 32 名 (39%) 威尔逊病患者的 H1069Q 突变为纯合子，39 名 (48%) 为杂合子（等位基因频率为 63%）。结合外显子 8 和 15 的序列分析，在 65% 的患者中发现了两个等位基因的突变。只有一名患者在其他部位同时存在两种突变。 H1069Q 纯合子中的症状比 H1069Q 复合杂合子 (14.6 +/- 5.8，P < 0.001) 或 H1069Q 阴性 (10 +/- 4.4，P < 0.001) 出现得晚 (21.3 +/- 7.2 年)，而且他们出现神经系统症状的频率更高 (93% vs. 47%，P < 0.001)和 Kayser-Fleischer 环（82 vs. 51%，P < 0.001）。突变状态与肝活检结果、血清铜蓝蛋白水平或 Cu-64 测定结果无关。结论：尽管存在许多已知的 ATP7B 突变，但在这个同质群体中只有少数发生。有限的基因检测有助于确认该人群的威尔逊病。 (C) 2001 年欧洲肝脏研究协会。由 Elsevier Science B.V. 出版。保留所有权利。
Background/Aims: Wilson disease is caused by a large number of different mutations in the ATP7B gene. Wilson disease patients from a homogeneous ethnical background (Saxonia) were studied for distribution and phenotypes of ATP7B mutations.Methods: Eighty-two patients were analyzed. The H1069Q mutation was assayed by a polymerase chain reaction-based restriction fragment length polymorphism test. Exons 8 and 15 were sequenced in all, and the entire gene in 30, non-H1069Q-homozygotes.Results: Four novel and 12 known mutations were found. Thirty-two (39%) Wilson disease patients were homozygous and 39 (48%) heterozygous for the H1069Q mutation (allele frequency 63%). Together with sequence analysis of exons 8 and 15 mutations in both alleles were identified in 65% of patients. Only one patient had both mutations at other locations. In H1069Q homozygotes symptoms started later (21.3 +/- 7.2 years) than in H1069Q compound heterozygotes (14.6 +/- 5.8, P < 0.001) or H1069Q negatives (10 +/- 4.4, P < 0.001), and they had more frequently neurologic symptoms (93 vs. 47%, P < 0.001) and Kayser-Fleischer rings (82 vs. 51%, P < 0.001). Mutation status did not correlate with liver biopsy findings, serum ceruloplasmin levels or Cu-64-assay results.Conclusions: In spite of many known ATP7B mutations, only few occur in this homogeneous population. Limited genetic testing is useful to confirm Wilson disease in this population. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.