Lysosomal Network Defects in Early-Onset Parkinson's Disease Patients Carrying Rare Variants in Lysosomal Hydrolytic Enzyme Genes.

ABSTRACT: Despite significant advances in understanding the genetics of Parkinson's disease (PD) and Parkinsonism, the diagnostic yield remains low. Pathogenic variants of GBA1, which encodes the lysosomal enzyme β-glucocerebrosidase and causes recessive Gaucher dis-ease, are recognized as the most important genetic risk factor for PD in heterozygous carriers. This study focuses on the functional genomics of rare genetic variations in other lysosomal hydrolytic enzymes genes in patient-derived fibroblasts. We examined 49 early-onset PD patients using whole exome sequencing and in silico panel analysis based on a curated PD gene list. Two patients were found to carry the p.Asp313Tyr variant in the X-linked GLA gene (encoding GALA, typically associated with Fabry disease), and one patien

SUBMITTER: Pascual A 

PROVIDER: S-EPMC12525278 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature