Exploring Genetic Influences On Variation In The Phenotypic Expression Of Parkinson’s Disease. (P2.029)

Objective: To investigate the influence of genotype on the phenotypic expression of Parkinson’s disease (PD). Background: A United Kingdom based multi-centre longitudinal study, the Parkinson’s Repository of Biosamples and Networked Datasets (PRoBaND), also known as Tracking Parkinson’s, is on-going. This is an interim report from the study. Methods: Testing was undertaken for common PD gene mutations. Validated clinical scales and questionnaires were used. Results: 191 early onset (diagnosed < 50 years old), and 548 late onset cases have been tested, out of 1860 recruited. 95% are Caucasian; two-thirds are male. In early onset cases, 19 (10%) tested positive (5 LRRK2, 11 GBA, 3 PARKIN), aged 51.6 (SD 6.2), disease duration 12.7 years (SD 8.8); and 173 (90%) tested negative, aged 52.6 (SD 8.3), disease duration 10.0 years (SD 6.6). The total unified PD rating scale (UPDRS) score in gene test positives was 70.4 (SD 26.8) vs 67.1 (SD 25.7) in gene test negatives; Montreal cognitive assessment (MOCA) score was 21.3 (SD 4.1) vs 22.3 (SD 3.5) , and quality of life (QOL) score was 36.1 (SD 17.3) vs 35.9 (SD 17.9). In late onset cases, 20 tested positive (3.7%) (6 LRRK2, 14 GBA), aged 59.5 (SD 13.4), disease duration 1.7 years (SD 1.0); and 528 tested negative (96.3%), aged 65.1(SD 13.1), disease duration 1.4 years (SD 1.0). The total UPDRS score in gene test positives was 48.5 (SD 21.6) vs 40.9 (SD 19.4) in gene test negatives; MOCA score was 21.5 (SD 5.8) vs 19.9 (SD 7.1), and QOL score was 19.3 (SD 14.2) vs 21.0 (SD 15.1). Conclusion: Early onset PD is more likely to test positive for known gene mutations, as expected. Further analysis extending the scope of genetic testing, and linked to progression rates, is planned. Supported by: Parkinson9s UK Disclosure: Dr. Malek has nothing to disclose. Dr. Marrinan has nothing to disclose. Dr. Bajaj has received personal compensation for activities with UCB Pharma and Eli Lilly & Company. Dr. Barker has received personal compensation for activities with Solvay S.A., Teva Neuroscience, Daniolabs, and Synosia. Dr. Ben-Shlomo has nothing to disclose. Dr. Bresner has nothing to disclose. Dr. Burn has received personal compensation for activities with Teva Neuroscience, Merck & Co. Inc., Serono Inc., and Boehringer Ingelheim Pharmaceuticals Inc. Dr. Burn has received research support from GlaxoSmithKline Inc. Dr. Foltynie has received personal compensation for activities with Abbvie, St Jude Medical, Medtronic Inc., Novartis. Dr. Morris has received personal compensation for activities with AbbVie, UCB Pharma, and Teva Neuroscience. Dr. Williams has nothing to disclose. Dr. Wood has nothing to disclose. Dr. Grosset has received personal compensation for activities with Civitas Inc., Vectura Group, and General Electric Healthcare. Dr. Grosset has received research support from Merz Pharma.