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Hepatology:年龄、性别,而非ATP7B 基因型影响Wilson疾病的临床表型

2018-09-25 MedSci MedSci原创

这些发现改进并扩展了对WD自然历史和WD临床表现的理解。一开始,无临床症状表现的患者可能会发展为有临床症状的患者。神经系统症状出现多年以后。

研究背景:Wilson(WD)是一种遗传性的肝铜代谢紊乱,临床表现有相当大的差异,最常见的是肝脏疾病和神经精神障碍。本研究调查了大量的WD患者的临床表现。

研究患者和方法:本研究共纳入1357例患者(702例儿童,655例成人;研究了1172例索引患者,185例兄弟姐妹,所有患者Leipzig得分≥4,男性/女性:679/678)。表现的年龄和症状被用作关键的表型标记。索引患者被归类为肝脏疾病(n=711)或神经系统疾病(n=461)。708(52.8%)例患者在诊断时做了肝活检。采用Genetic Analyzers ABI Prism 310 (Perkin Elmer)或 3500 (Applied Biosystems)进行DNA测序。

主要研究结果:1:研究共发现了394种不同的突变组合。最常见的突变类型为H1069Q (c.3207C>A; 等位基因频率: 46.9%), 随后为 P767P-fs (c.2304dupC; 2.85%), P1134P-fs (c.3402delC; 2.8%)和 R969Q (c.2755C>T; 2.18%)。2:突变和个体患者临床表现,没有相关性。3:在索引患者中发现有性别效应:在女性中,肝脏表现更为常见(m/f:328/383)和在男性中,神经系统表现(259/202;p < 0.001)。4:在诊断时,39.5%的患者为儿童/青少年(18),但58%的成年人患有肝硬化。肝硬化的存在与基因型没有关系。

研究结论:这些发现改进并扩展了对WD自然历史和WD临床表现的理解。一开始,无临床症状表现的患者可能会发展为有临床症状的患者。神经系统症状出现多年以后。

原始出处

Ferenci P, Stremmel W, Czlonkowska A, et al. Age,sex, but not ATP7B genotype effectively influences the clinical phenotype of Wilson disease. Hepatology, 2018,

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    2018-11-14 zll0625
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    2018-09-27 gwc384
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    2018-09-27 listen320
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    2018-09-27 tastas

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