Institute of Neurogenomics, Helmholtz Zentrum München, Munich, Germany.
Institute of Human Genetics, Technical University of Munich, Munich, Germany.
Mov Disord. 2021 Aug;36(8):1959-1964. doi: 10.1002/mds.28614. Epub 2021 May 5.
Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications.
We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity).
We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses.
Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81.
The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
尽管基因组检测策略具有既定的价值，但在许多情况下，其实践指南并不存在。
我们旨在验证一种最近引入的用于预测基于个体表型特征（发病年龄、身体分布、伴发的合并症）的全外显子组测序（WES）诊断效用的肌张力障碍评分算法。
我们前瞻性地招募了一组 209 个受肌张力障碍影响的家族，并根据该算法获得了综合评分（0-5 分）。对单卵（N=146）、双卵（N=11）和三卵（N=52）WES 数据进行了生成，以识别遗传诊断。
综合评分最高（5 分）的个体的诊断率最高（51%），对应于早发性节段性或全身性肌张力障碍伴同时存在非运动障碍相关的神经系统症状的表现。先前建议实施 WES 的阈值（3 分）的敏感性和特异性为 96%和 52%，曲线下面积为 0.81。
该算法是一种有用的预测工具，可整合到肌张力障碍的常规诊断方案中。© 2021 作者。运动障碍由 Wiley 期刊代表国际帕金森运动障碍协会出版。
