DCTN1 F52L mutation case of Perry syndrome with progressive supranuclear palsy-like tauopathy.
DCTN1 F52L mutation case of Perry syndrome with progressive supranuclear palsy-like tauopathy.
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DOI：
10.1016/j.parkreldis.2018.02.038
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发表时间：
2018-06
影响因子：
4.1
通讯作者：
H. Honda;N. Sasagasako;C. Shen;Masahiro Shijo;Hideomi Hamasaki;Satoshi O. Suzuki;Y. Tsuboi;N. Fujii;T. Iwaki
中科院分区：
文献类型：
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作者：
H. Honda;N. Sasagasako;C. Shen;Masahiro Shijo;Hideomi Hamasaki;Satoshi O. Suzuki;Y. Tsuboi;N. Fujii;T. Iwaki
Perry综合征是一种进展迅速的常染色体显性帕金森综合征，以中枢性通气不足、抑郁和严重体重减轻为特征。到目前为止，已经确定了8个DCTN 1突变与佩里综合征相关。一种新的F52 LDCTN 1突变的情况下，佩里综合征的特点是迟发性帕金森综合征和额颞叶atrophic atrophic.MethodsA日本妇女患有缓慢进展的帕金森综合征，因为48岁。59岁时，她出现中枢性换气不足，需要呼吸辅助。基因分析发现DCTN 1中存在p.F52L突变，诊断为佩里综合征。结果尸检发现黑质和壳核神经元严重缺失。DCTN 1的免疫组化显示许多异常聚集，主要在脑干和基底神经节的神经元。此外，在基底节、脑干和小脑中观察到许多异常的磷酸化tau蛋白沉积，包括神经元缠结、簇状星形胶质细胞和卷曲体。这些符合进行性核上性麻痹的神经病理学标准。偶见DCTN 1和tau蛋白共定位。磷酸化的α-synuclein和DCTN 1也在眼神经核的Lewy小体样结构中共定位。磷酸化TARDBP阳性神经元胞质包涵体很少。ConclusionIn与长期疾病的持续时间和老化，我们的研究结果表明，F52 LDCTN 1突变可能会引起严重的tau蛋白病和中度α-突触核蛋白病。
IntroductionPerry syndrome is a rapidly progressive, autosomal dominant parkinsonism characterized by central hypoventilation, depression and severe weight loss. To date, eight DCTN1 mutations have been identified associated with Perry syndrome. A novel F52LDCTN1mutation case of Perry syndrome is characterized by late-onset parkinsonism and frontotemporal atrophy.MethodsA Japanese woman suffered from slowly progressing parkinsonism since age 48. At age 59, she developed central hypoventilation, and required breathing assistance. Gene analysis identified a p.F52L mutation inDCTN1and she was diagnosed with Perry syndrome. She died of aspiration pneumonia at age 74.ResultsPostmortem examination revealed severe neuronal loss in the substantia nigra and the putamen. Immunohistochemistry for DCTN1 revealed many abnormal aggregates, mainly in neurons in the brainstem and basal ganglia. Additionally, numerous abnormal phosphorylated tau deposits including neurofibrillary tangles, tuft-shaped astrocytes and coiled bodies were observed mainly in the basal ganglia, brainstem and cerebellum. These correspond with the neuropathologic criteria for progressive supranuclear palsy. Colocalization of DCTN1 and tau were occasionally seen. Colocalization of phosphorylated α-synuclein and DCTN1 were also observed in Lewy body-like structures in oculomotor nuclei. Phosphorylated TARDBP-positive neuronal cytoplasmic inclusions were few.ConclusionIn conjunction with long disease duration and aging, our findings suggest that the F52LDCTN1mutation may evoke severe tauopathy and moderate α-synucleinopathy.