DCTN1 F52L mutation case of Perry syndrome with progressive supranuclear palsy-like tauopathy. (June 2018)

• Record Type: Journal Article
• Authors: Honda, Hiroyuki; Sasagasako, Naokazu; Shen, Chang; Shijo, Masahiro; Hamasaki, Hideomi; Suzuki, Satoshi O.; Tsuboi, Yoshio; Fujii, Naoki; Iwaki, Toru
• Is Part Of: Parkinsonism & related disorders. Volume 51(2018)
• Page Start: 105
• Page End: 110
• Publication Date: 2018-06
• Subjects: Perry syndrome -- DCTN1 -- Dynactin -- Tauopathy -- Progressive supranuclear palsy; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2018.02.038
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Introduction: Perry 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 F52L DCTN1 mutation case of Perry syndrome is characterized by late-onset parkinsonism and frontotemporal atrophy. Methods: A 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 in DCTN1 and she was diagnosed with Perry syndrome. She died of aspiration pneumonia at age 74. Results: Postmortem 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. Conclusion: In conjunction with long disease duration and aging, our findings suggest that the F52L DCTN1 mutation may evoke severe tauopathy and moderate α-synucleinopathy. Highlights: Perry syndrome is a rapidly progressive, autosomal dominant parkinsonism characterized by central hypoventilation and severe weight loss. F52L Perry syndrome shows distinctive features such as late-onset, long disease duration and frontotemporal atrophy. In this autopsy study, we demonstrated variety of DCTN1 aggregates, many neurofibrillary tangles and glial tau correspond with progressive supranuclear palsy. Co-localization of p-tau and DCTN1 was noted in neurofibrillary tangles and dystrophic neurites. This is the first report of Perry syndrome with tauopathy, suggesting correlation between dynactin and tauopathy.