Paudel Reema, Li Abi, Hardy John, Bhatia Kailash P, Houlden Henry, Holton Janice
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Neurodegener Dis. 2016;16(3-4):273-8. doi: 10.1159/000440863. Epub 2015 Nov 27.
Mutations in the thanatos-associated protein domain containing apoptosis-associated protein 1 gene (THAP1) are responsible for adult-onset isolated dystonia (DYT6). However, no neuropathological studies of genetically proven DYT6 cases have been previously reported.
We report the first detailed neuropathological investigation carried out on two DYT6 brains.
Genetic screening for THAP1 gene mutations using standard Sanger polymerase chain reaction sequencing identified 2 cases, 1 with a known pathogenic mutation and the other with a novel mutation. A detailed neuropathological assessment of the cases was performed.
Both DYT6 cases showed no significant neurodegeneration and no specific disease-related pathology.
No neuropathological features that could be defined as hallmark features of DYT6 dystonia were identified. Our study supports the notion that in isolated dystonia, there is no significant neurodegeneration or morphological lesions that can be identified using routine methods.
含凋亡相关蛋白1基因（THAP1）的死亡相关蛋白结构域突变是成人起病的孤立性肌张力障碍（DYT6）的病因。然而，此前尚未有关于经基因证实的DYT6病例的神经病理学研究报道。
我们报告了对两个DYT6病例大脑进行的首次详细神经病理学研究。
使用标准桑格聚合酶链反应测序对THAP1基因突变进行基因筛查，确定了2例病例，1例有已知致病突变，另1例有新突变。对这些病例进行了详细的神经病理学评估。
两个DYT6病例均未显示明显的神经退行性变，也未发现特定的疾病相关病理学改变。
未发现可定义为DYT6肌张力障碍标志性特征的神经病理学特征。我们的研究支持这样一种观点，即在孤立性肌张力障碍中，不存在可通过常规方法识别的明显神经退行性变或形态学病变。
