Abstract
Background Monogenic Parkinson’s disease (PD) accounts for 14% of PD and a higher proportion of familial and early-onset cases. MonoPDAus is a MRFF-funded study of monogenic PD in Australia which aims to: i) improve genetic diagnosis, gene discovery and laboratory evaluation of genetic variants, ii) characterise clinical phenotypes, disease progression and treatment responses, iii) assess clinical, personal, and familial utility of genomic testing, iv) evaluate cost-effectiveness of genomic testing, and v) establish an Australian monogenic PD patient registry, enabling rapid recruitment to future clinical trials. MonoPDAus harnesses the broad reach of the Australian Parkinson’s Genetic Study (APGS), which has recruited over 7000 Australian individuals with PD, and the sequencing power of the Global Parkinson’s Genetics Program (GP2).
Methods APGS participants with early-onset and/or familial PD will be offered participation in MonoPDAus, supplemented by direct recruitment, aiming for 1000 probands. Participants undergo telehealth assessments at baseline, 18 and 36 months and surveys to assess utility of and attitudes toward genomic testing. Whole genome sequencing will be performed through GP2 and genetic results returned to participants. Cost-effectiveness will be assessed.
Results Approximately 2200 APGS participants are eligible for MonoPDAus based on onset age and family history. Recruitment from APGS to MonoPDAus will commence this year. Direct recruitment to the GP2 Monogenic Network has commenced (n = 50) – sequencing data for these participants is undergoing variant filtration.
Conclusion By offering the genetic sequencing capabilities of GP2 to a large Australian PD population, MonoPDAus promises to provide a comprehensive characterisation of monogenic PD.
