Genetic Analysis of RAB39B in an Early-Onset Parkinson's Disease Cohort

This study aimed to investigate the contribution of the genetic variation in RAB39B to the development of early-onset PD. We performed gene dosage studies and sequence analysis in a cohort of 176 individuals with early-onset PD (age of onset ≤ 50 years) of unknown genetic etiology. An assessment of the copy number variation over both coding exons and the 3′ untranslated region (UTR) of RAB39B did not identify any alterations in gene dosage. An analysis of the UTRs identified two male individuals carrying single, likely benign, nucleotide variants in the 3′UTR (chrX:154489749-A-G and chrX:154489197-T-G). Furthermore, one novel variant of uncertain significance was identified in the 5′UTR, 229 bp upstream of the start codon (chrX:154493802-C-T). In silico analyses predicted that this variant disrupts a highly conserved transcription factor binding site and could impact RAB39B expression. The results of this study do not support a significant role for genetic variation in RAB39B as contributing to early-onset PD but do highlight that additional molecular studies are required to determine the mechanisms regulating RAB39B expression and their association with the disease. Genetic investigations in larger parkinsonism/PD cohorts and longitudinal studies of individuals with cognitive impairment due to an altered dosage of RAB39B will be required to fully delineate the contribution of RAB39B to parkinsonism.
Source: Frontiers in Neurology - Category: Neurology Source Type: research