Institute of Neurogenetics, University of Lübeck, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy.
Parkinsonism Relat Disord. 2021 May;86:101-104. doi: 10.1016/j.parkreldis.2021.03.028. Epub 2021 Apr 20.
Heterozygous carriers of Parkin mutations are suggested to be at risk of developing Parkinson's disease, while biallelic variants are associated with typical autosomal recessive early-onset PD. Investigating unaffected heterozygous mutation carriers holds the potential of a deeper understanding of monogenic PD and has implications for PD in general, in particular regarding the prodromal phase.
To discriminate healthy Parkin mutation carriers from healthy non-mutation carriers using a multimodal approach.
Twenty-seven healthy heterozygous Parkin mutation carriers (13 female. age: 48 ± 13 years) and 24 healthy non-mutation carriers (14 female. age: 48 ± 15 years) from the CHRIS study (Cooperative Health Research in South Tyrol) were recalled based on their genetic profile and underwent a blinded assessment of motor and non-motor PD symptoms, transcranial sonography and sensor-based posturography and gait analyses under different conditions with increasing difficulty. For the latter, gradient-boosted trees were used to discriminate between carriers and non-carriers. The classification accuracy and the area under the curve of the receiver-operator characteristics curve were calculated.
We observed no differences concerning motor or non-motor symptoms and substantia nigra hyperechogenicity. The best gradient-boosted trees-based model on posturography measurements (tandem feet, eyes closed, firm surface), however, showed a classification accuracy of up to 86%. The best-performing gradient-boosted trees-based model for gait analyses showed a balanced accuracy of up to 87% (dual-tasking).
Sensor-based quantification of movements allows to discriminate unaffected heterozygous mutation carriers from mutation-free controls. Thereby, it is crucial to challenge the motor system with more difficult tasks to unmask subtle motor alterations.
杂合子 Parkin 突变携带者被认为有患帕金森病的风险，而纯合子变体则与典型的常染色体隐性早发性 PD 相关。研究未受影响的杂合子突变携带者有可能更深入地了解单基因 PD，并对一般 PD 产生影响，特别是在前驱期。
使用多模态方法区分健康的 Parkin 突变携带者和健康的非突变携带者。
根据基因谱，从 CHRIS 研究（南蒂罗尔合作健康研究）中召回了 27 名健康的杂合子 Parkin 突变携带者（13 名女性，年龄：48 ± 13 岁）和 24 名健康的非突变携带者（14 名女性，年龄：48 ± 15 岁），并对他们进行了运动和非运动 PD 症状、经颅超声和基于传感器的姿势和步态分析的盲评，测试条件逐渐增加难度。对于后者，使用梯度提升树来区分携带者和非携带者。计算分类准确性和接收器操作特性曲线的曲线下面积。
我们观察到携带者和非携带者在运动或非运动症状和黑质回声强度方面没有差异。然而，基于姿势测量（双脚并拢、闭眼、坚固表面）的最佳梯度提升树模型的分类准确性高达 86%。对于步态分析，表现最好的梯度提升树模型的平衡准确性高达 87%（双重任务）。
基于传感器的运动量化可区分未受影响的杂合子突变携带者和无突变对照者。因此，通过更困难的任务来挑战运动系统以揭示细微的运动改变至关重要。
