Vacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset autosomal dominant Parkinson’s disease (PD). However, VPS35 mutations are rarely reported in Asian populations. Herein, we report the first Taiwanese family with the pathogenic VPS35 p.D620N mutation, including one patient treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS). A 61-year-old woman presented with progressive left hand resting tremor at the age of 42. Neurological examinations revealed mask face and akinetic-rigidity over left extremities. She showed a good response to levodopa treatment, and her unified Parkinson’s disease rating scale (UPDRS) motor scores improved from 42 to 15 under the levodopa equivalent dose of 1435 mg/day. She developed peak-dose dyskinesia and motor fluctuation seven years after the onset of symptoms, and received bilateral STN-DBS at the age of 55. Stimulation led to a marked improvement in her motor symptoms with a 37% improvement in the UPDRS motor score during the OFF period five years after surgery. The patient’s mother and three siblings were also diagnosed with PD in their forties, following an autosomal-dominant inheritance pattern. We performed genetic analysis of the proband using a targeted next generation sequencing (NGS) panel covering 17 known PD-causative genes. We identified a pathogenic missense mutation in VPS35 gene, c.1858G > A (p.D620N), in this patient. This is the first report of the VPS35 p.D620N mutation in a Taiwanese family. Additionally, our report contributes to the current understanding of genetically defined PD patients treated successfully with STN-DBS.

Background/purpose: A heterozygous three-nucleotide (GAG) in-frame deletion in the TOR1A gene causes the rare disease, dystonia (DYT1), which typically presents as focal limb dystonia during adolescence, then spreads to other limbs. This study investigated the frequency and clinical features of DYT1 in a Taiwanese dystonia cohort. Methods: We performed targeted next generation sequencing in 318 patients with primary dystonia. We identified one DYT1 family with various types of dystonia, and we described the clinical presentations observed in this family during a 30-year follow-up. We compared the clinical characteristics to those reported in previous studies on DYT1 from 2000 to 2020. Results: Among 318 patients, we identified only one DYT1 patient (0.3%) with an autosomal dominant family history of dystonia. The proband was a 43-year-old man that experienced progressive onset of focal lower limb dystonia from age 11 years. The disease spread caudalrostrally to the upper limbs and cervical muscles. Prominent cervical dystonia was noted during follow-up, which was an atypical presentation of DYT1. Clinical assessments of other family members showed intrafamily variability. The proband's father and an affected sibling demonstrated only mild right-hand writer's cramp. A systematic review of previously reported DTY1 cases showed that Asian patients had a higher frequency of cervical dystonia (44.8%) than groups of Ashkenazi Jews (35%) and Non-Jewish Caucasians (30.5%) (P Z 0.04). Conclusion: Our findings revealed that DYT1 is rare in a Taiwanese dystonia cohort. The pre-sentation of marked cervical dystonia could be the main feature of Asian patients with DYT1. Copyright 2021, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Depression is a common comorbidity in patients with Parkinson’s disease (PD) and in their caregivers. This study aimed to compare the prevalence and risk factors of depression between patients with PD and their caregivers. In total, 113 patients with PD and 101 caregivers were enrolled. Patients with PD were assessed using the Mini International Neuropsychiatric Interview, Unified Parkinson’s Disease Rating Scale (UPDRS), Activities of Daily Living (ADL), Hospital Anxiety and Depression Scale, Beck Hopelessness Scale, Brief Fatigue Inventory, Connor–Davidson Resilience Scale, and Big Five Inventory-10. Caregivers of patients with PD were also assessed using the above-mentioned instruments, with the exception of the UPDRS and ADL. During a 12-month follow-up period, depressive disorders were the most common psychiatric diagnosis of PD patients (27.4%) and their caregivers (17.8%). Depressive disorders were more prevalent in PD patients than in caregivers of PD patients throughout the entire follow-up phase. The severity of fatigue and severity of suicide risk were significantly associated with depression among patients with PD. The severity of pain and severity of anxiety were predictors of depression in caregivers of PD patients. The findings in this study provide references for early detection and treatment of depressive disorders in PD patients and their caregivers.