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Background Parkinson’s disease (PD) is a common neurodegenerative disorder, for which genetics plays a small yet significant component of its complex aetiology. Copy number variants (CNVs), involving duplications or deletions of DNA segments of varying length, are increasingly recognised to contribute to PD pathogenesis and risk. Aims The present study investigated CNV prevalence in 191 PD patients from across the country (175 autosomal dominant, 3 autosomal recessive, 13 sporadic). Additionally, 10 PD patients with previously identified PARK2 mutations were analysed for second mutations which would indicate compound heterozygous states. Methods Multiplex ligation-dependent probe amplification (MLPA) was used to identify CNVs in known PD genes, using SALSA P051 and P052 probe kits (MRC Holland), which contained probes for all exons of SNCA, PARK2, UCLH1, PINK1, DJ-1, LRRK2 and ATP13A2. Raw data was analysed using GeneMapper Software, with deletion/duplication boundaries delineated by ≤0.75 and≥1.25 ratio values respectively. Results A total of 11 exon duplications/deletions in the PD genes PARK2, SNCA, DJ-1 and PINK1 were identified, indicating that 5% of our PD cohort possessed CNVs. Significant findings include 3 whole gene SNCA duplications, a heterozygous PARK2 exon 2 deletion in a pseudo-dominant PD patient, a novel heterozygous DJ-1 duplication of exons 2,3,5,6,7 and a novel homozygous PINK1 deletion of exon 1. Conclusions Whilst further clinical and genetic information requires incorporation with our findings, the present study emphasises the importance of CNV detection in PD, and contributes to current work exploring the role of single heterozygous PARK2 CNVs in PD risk.

Background Parkinson’s disease (PD) is associated with motor and non-motor symptoms, including cognitive impairment. Genetic features may influence clinical symptoms. Objective Familial PD patients have been recruited through the ABN British Neurological Surveillance Unit (BNSU) to the Parkinson’s Families Project. A primary aim of this study is to examine how genetic factors influence phenotype. We present baseline clinical data and a description of cognitive impairment in familial PD patients from this cohort. Methods Eligible patients are referred through the BNSU. Blood samples are collected for DNA. Systematic clinical data is collected using a similar approach to the Tracking Parkinson’s (PRoBaND) study. Results 101 patients with familial PD have been recruited to date from participating hospitals or remotely. Cognitive outcomes were assessed in the Montreal Cognitive Assessment (MoCA). In the first 85 familial PD patients, 27.1% of patients met criteria for mild cognitive impairment, 10.6% patients met criteria for severe cognitive impairment, and 62.4% of patients had normal cognition. Analysis of genetic data is underway and results with rare Mendelian mutations will be reported. Conclusions The BNSU is an essential source of recruitment to the Parkinson’s Families Project. Identification of genetic factors that influence phenotype will lead to new drug targets.

The Parkinson9s Families Project is a multi-centre genetic epidemiology study. Aims To identify new genetic variants that predispose to or cause familial or early onset PD. Methods Families with either familial or early onset PD are recruited. The ABN BNSU is a source of participant recruitment, by which patients with familial PD from across the UK can be notified to the study team monthly by ABN members. Permission to contact the patient is obtained from the patient through the consultant. Following informed consent, patients provide blood samples for genetic analysis and complete standard study questionnaires. Results (April 2015–Jan 2016): Over 10 months we have received 96 BNSU referrals (mean 10/month) from 33 consultants. We have received 35 permission-to-contact forms from patients (36.5%) and 19 patients/families have completed study enrollment (19.8% recruitment rate). Conclusions The BNSU is an invaluable source of referral for patients with rare diseases from across the UK, and we currently have a 20% patient recruitment rate. However, there is a delay from study initiation to completion of patient recruitment. We could improve the relatively low rate of patient contact by establishing a formal system of regular follow-ups for consultants and an anonymised tracking system for BNSU-referred patients. Finally, we suggest the possibility of multi-source recruitment through Parkinson9s UK, local study sites, geriatricians and PD nurses.