PO184 Analysis of copy number variants in familial and sporadic parkinson’s disease

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.