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

Abstract

BackgroundVacuolar 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 presentationA 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.ConclusionsThis 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.

Deep Brain Stimulation in Patients With Mutations in Parkinson's Disease–Related Genes: A Systematic Review

“…At the shorter follow‐up (n = 2), the improvement was marked (76%) or satisfactory (36%) . Satisfactory improvement was still seen at intermediate and longer term follow‐up: 37.1% at 5 years and 43.8% at 8 years, respectively. LEDD was largely reduced in 1 study by around 70% (including at longer term), and decreased by 30.3% (at 1 year) and 19.2% (at 5 years) in the other study …”

“…The 25 articles included reported 151 patients with PD‐related mutations (2 patients are represented twice in Angeli and colleagues); from which 135 patients were included in the outcome analysis. The selected articles included PRKN , LRRK2 , Phosphatase and tensin homolog ( PTEN )‐induced putative kinase 1 ( PINK1 ), GBA , alpha‐synuclein ( SNCA ) and retromer complex component ( VPS35 ) mutations in addition to chromosome 22q11.2 microdeletion. Age at onset ranged from 10 to 57 years old, and the duration of disease at DBS implant ranged from 4 to 45 years .…”

“…A total of 3 patients with the VPS35 mutation underwent STN‐DBS and were followed for 1 to 8 years . At the shorter follow‐up (n = 2), the improvement was marked (76%) or satisfactory (36%) .…”

A clinical and genetic study of early‐onset and familial parkinsonism in taiwan: An integrated approach combining gene dosage analysis and next‐generation sequencing

“…B). We also identified 2 probands (1.4%) carrying VPS35 mutations, 1 with the previously reported p.D620N and another with the p.S679P mutation (Supplementary Fig. 2C).…”

Deep brain stimulation for monogenic Parkinson’s disease: a systematic review

“…Four studies [51][52][53][54] reported five patients (STN n = 3, NA n = 2). Favourable motor outcome was reported in four cases and minor motor benefit complicated by dysarthria in one case.…”