A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length
A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length
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DOI：
10.1111/j.1399-0004.2004.00241.x
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发表时间：
2004-04-01
影响因子：
3.5
通讯作者：
Hayden, MR
中科院分区：
文献类型：
--
作者：
Langbehn, DR;Brinkman, RR;Hayden, MR
亨廷顿病（HD）是一种由不稳定的CAG重复序列引起的神经退行性疾病。对于有风险的患者，参与预测性测试并了解CAG扩展，一个主要的未回答的问题从“我会得到HD吗？“到“什么时候会显现？“使用迄今为止分析的最大HD患者队列（来自全球40个中心的2913名患者），我们开发了一个基于CAG重复长度的参数生存模型，以预测神经系统疾病发病的可能性（基于运动神经症状而不是精神病发病）在不同年龄的个体患者。我们提供了估计发病概率与CAG重复36和56之间的任何年龄段的个人狭窄的置信区间。例如，我们的模型预测一个40岁的个体有91%的机会在65岁时发病，95%的置信区间为90%至93%。该模型还定义了HD发作的变异性，该变异性不归因于CAG长度，并提供了关于CAG相关的再发率的信息。
Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. For patients at risk, participating in predictive testing and learning of having CAG expansion, a major unanswered question shifts from "Will I get HD?" to "When will it manifest?" Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. For example, our model predicts a 91% chance that a 40-year-old individual with 42 repeats will have onset by the age of 65, with a 95% confidence interval from 90 to 93%. This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates.