Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT, USA.
Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, Yale University, New Haven, CT, USA.
Ann Neurol. 2020 Nov;88(5):1028-1033. doi: 10.1002/ana.25863. Epub 2020 Aug 22.
PPP2R5D-related neurodevelopmental disorder is characterized by a range of neurodevelopmental and behavioral manifestations. We report the association of early-onset parkinsonism with the PPP2R5D p.E200K mutation. Clinical characterization and exome sequencing were performed on three patients, with postmortem neuropathologic examination for one patient. All patients had mild developmental delay and developed levodopa-responsive parkinsonism between the ages of 25 and 40 years. The PPP2R5D c.598G>A (p.E200K) mutation was identified in all patients. Neuropathologic examination demonstrated uneven, focally severe neuronal loss and gliosis in the substantia nigra pars compacta, without Lewy bodies. Our findings suggest the PPP2R5D p.E200K mutation to be a possible new cause of early-onset parkinsonism. ANN NEUROL 2020;88:1028-1033.
PPP2R5D 相关性神经发育障碍的特征是一系列神经发育和行为表现。我们报告了 PPP2R5D p.E200K 突变与早发性帕金森病的关联。对 3 名患者进行了临床特征分析和外显子组测序，并对 1 名患者进行了死后神经病理学检查。所有患者均有轻度发育迟缓，在 25 至 40 岁之间出现左旋多巴反应性帕金森病。在所有患者中均发现 PPP2R5D c.598G>A（p.E200K）突变。神经病理学检查显示黑质致密部神经元丢失和神经胶质增生不均匀，局灶性严重，无路易体。我们的研究结果提示 PPP2R5D p.E200K 突变可能是早发性帕金森病的一个新的潜在病因。神经病学年鉴 2020；88:1028-1033.
