Identification of PLA2G6 variants in a Chinese patient with Parkinson's disease

Parkinson’s disease (PD) is a clinical syndrome and a heterogeneous group of neurodegenerative conditions with variable pathologies and clinical sub-entities, characterized by motor symptoms and non-motor features. PD represents an outcome of the combination of genes and other risk or protective factors. Patients with variants in the phospholipase A2 group VI gene (PLA2G6) can present complex Parkinsonian phenotypes. This study reported a PD patient with typical motor symptoms of PD, including bradykinesia, gait disturbance, rigidity, and rest tremor, who also suffered from nocturia, constipation, and sleeping problems. Two PLA2G6 variants, c.402C>T and c.2327_2328del, were identified in the patient by whole exome sequencing followed by Sanger sequencing. The transition c.402C>T was predicted to generate an alternative acceptor splice site, though the minigene splicing assay showed negative in vitro outcomes. The novel variant c.2327_2328del was predicted to result in a truncated protein. These two variants may be pathogenic in PD or increase the susceptibility to PD individually or collaboratively. This discovery may enrich the genetic landscape of PLA2G6-associated PD and confirm the notion of prioritizing whole exome sequencing analysis in patients with PD.