Identification of VPS35 p.D620N mutation-related Parkinson's disease in a Taiwanese family with successful bilateral subthalamic nucleus deep brain stimulation: A case report and literature review
Journal
BMC Neurology
Journal Volume
17
Journal Issue
1
Date Issued
2017
Author(s)
Abstract
Background: 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). Case presentation: 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. Conclusions: 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. ? 2017 The Author(s).
SDGs
Other Subjects
levodopa; unclassified drug; vacuolar protein sorting 35; vesicular transport protein; VPS35 protein, human; adult; aged; akinesia; Article; autosomal dominant inheritance; brain depth stimulation; case report; clinical article; drug response; dyskinesia; family study; female; gene; gene identification; genetic analysis; hand tremor; human; male; missense mutation; motor dysfunction; neurologic examination; next generation sequencing; Parkinson disease; subthalamic nucleus; Taiwanese; Unified Parkinson Disease Rating Scale; VPS35 gene; Asian continental ancestry group; brain depth stimulation; dyskinesia; genetic screening; genetics; high throughput sequencing; middle aged; mutation; Parkinson disease; procedures; subthalamic nucleus; treatment outcome; Asian Continental Ancestry Group; Deep Brain Stimulation; Dyskinesias; Female; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Levodopa; Middle Aged; Mutation; Parkinson Disease; Subthalamic Nucleus; Treatment Outcome; Vesicular Transport Proteins
Publisher
BioMed Central Ltd.
Type
journal article