Two Novel Variants of VPS13C Gene Related Parkinsonism: A Case Report and Literature Review

Yanyan JiangChenghe Fan^*

• Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China

Background: Mutations in the Vacuolar Protein Sorting 13 Homolog C (VPS13C) gene have been associated with early-onset Parkinson's disease and dementia with Lewy bodies. However, these mutations are rare in Parkinson's disease. This study aimed to report the clinical and genetic features of VPS13C-related parkinsonism. Methods: The patient first exhibited resting tremor in the right limb at the age of 26. As the disease progressed, he developed bradykinesia, rigidity, gait instability, cognitive decline, dysarthria, myoclonus, depressed mood, irritability, and aggression. Follow-up brain magnetic resonance imaging showed progressive cortical atrophy. Whole-exome sequencing was performed to identify the genetic cause, co-segregation analysis of candidate variants was conducted in the patient's family. Additionally, we reviewed 20 previously reported cases of VPS13C-related parkinsonism. Results: Whole-exome sequencing of the patient revealed compound heterozygous pathogenic variants (c.1699C >T, chr15: 62156504-62352664) in VPS13C. The presence of deletions affecting exons 13, 14, and 35 was confirmed using quantitative polymerase chain reaction. A review of the literature indicates that VPS13C-related parkinsonism appears as a heterogeneous disorder, including Parkinson's disease and dementia with Lewy bodies. VPS13C mutations are highly diverse, with point mutations being the most common, followed by splice-site variants. Conclusions: This study identifies two novel pathogenic variants in VPS13C, expanding the known mutational spectrum of the gene. Additionally, brain magnetic resonance imaging may serve as a potential imaging marker for disease progression.