s / Parkinsonism and Related Disorders 22 (2016) e149ee192 e171 Objectives: PD is an emerging class of autosomal mitochondrial diseases account for a rapidly growing clinical group. Until recently, it was thought that primary mtDNA mutations were the major cause of mitochondrial disease in humans, particularly those presenting in adult life. The proposed research work would plan to analyze the genetics and molecular basis in the POLG mutations in the gene encoding for mtDNA in PD patients. Methods: The PD patient group comprised of 30 individuals and equal numbers of control groups were selected. We collected risk factor information by in-person interview personally with informed concern form. POLG gene polymorphisms were detected using a PCReRFLP technique. Odds ratios were estimated using logistic regression Results: We observed the increased risk of PD among carriers of the homozygous variant genotype of POLG (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.10-4.03) and the homozygous variant genotype of (OR, 1.3; 95% CI, 0.50-6.53). Conclusion: In conclusion my work would involve indicating the neurological diseases which share some common clinical and etiological features with different molecular mechanisms underlie in the observed PD patients. Furthermore, biochemical studies will also help to unravel the mechanisms of pathogenesis, and patterns to emerge relating genotype to phenotype. Therefore, new treatments with the therapeutic target of improving mitochondrial function may prove to be promising. P 5.019. ASSOCIATION OF MORTALIN (HSPA9) AND OTHER MITOCHONDRIARELATED GENES WITH THE RISK OF PARKINSON'S DISEASE AND ALZHEIMER'S DISEASE Sun Ju Chung , Mi-Jung Kim , Ho-Sung Ryu , Juyeon Kim , Young Jin Kim , Kiju Kim , Sooyeoun You , Seong Yoon Kim , Jae-Hong Lee . Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Neurology, Bobath Memorial Hospital, Seongnam, Republic of Korea; Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Neurology, Dongsan Medical Center, Keimyung University, Daegu, Republic of Korea; Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Objectives: To investigate the role of genetic variants of the HSPA9 (mortalin gene) in the risk of Parkinson's disease (PD) and Alzheimer's disease (AD) as well as their genetic interactions with other mitochondriarelated genes. Methods: The mortalin (HSPA9), parkin, PINK1, DJ1, and COQ2 genes were selected. For HSPA9, direct sequencing was performed in 24 AD patients, 24 PD patients, and 24 controls. Common and low-frequency genetic variants were also selected using the HapMap and 1000 Genomes Project JPT and CHB samples to select variants in the HSPA9, parkin, PINK1, DJ1, and COQ2 genes. We genotyped genetic variants (8 in HSPA9, 10 in parkin, 4 in PINK1, 6 in DJ1, and 2 in COQ2) in 400 AD cases, 500 PD cases, and 500 controls, using the Fluidigm high-throughput platform. Results: The high-risk group carrying more than 4 risk alleles in the HSPA9 SNP rs41295739, parkin SNP rs9356040, PINK1 SNP rs76795760, DJ1 SNP rs2235733, and COQ2 variant M128V had significantly increased risk of PD compared with the low-risk group carrying 0-2 risk alleles (c2 1⁄4 0.01). The high-risk group carrying more than 3 risk alleles in the HSPA9 SNP rs41295739, parkin SNP rs1784590, PINK1 SNP rs1043424, DJ1 SNP rs34124834, and COQ2 SNP rs148156462 had significantly increased risk of AD comparedwith the low-risk group carrying 0-2 risk alleles (c21⁄4 0.039). Conclusions: Our results suggest that genetic interaction among mitochondria-linked genes may play a role in the development of PD and AD. P 5.020. SCREENING OF SPONTANEOUS GENOMIC ALTERATIONS AND P53 GENE POLYMORPHISM IN NEW ONSET OF PARKINSON DISEASE Jayalakshmi Ramalingam , Iyer mahalaxmi , Mohanadevi Subramaniam , Lokesh Thangamani , Arun Meyyazhagan , Balachandar Vellingiri . Department of Human Genetics and Molecular Biology, School of Life Sciences, Bharathiar University, 641046, Tamil Nadu, South India, Coimbatore, India; Human Genetics Laboratory, School of Life Sciences, Bharathiar University, 641046, Tamil Nadu, South India, Coimbatore, India; BHMG Research and Diagnostic Laboratory, Kovaipudur, Coimbatore, 641042, Tamil Nadu, South India, Coimbatore, India Objectives: Parkinson's disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. To evaluate the presence of spontaneous chromosomal alterations, Micronucleus, and p53 polymorphism at codon 72 in peripheral blood leukocytes in newly diagnosed Parkinson patients. Methods: Patients with Parkinson disease (35) and control subjects (35), was recruited and matched for age, sex, and smoking habits. Cytogenetic analysis was performed using the human lymphocyte for finding Chromosomal alterations and micronucleus assay. Restriction Fragment Length Polymorphism was done for genotype analysis of P53 gene. Results: Patients with Parkinson disease showed an increase in the incidence of spontaneous Chromosomal alterations (p < 0.05); micronuclei (p < 0.05) compared to controls. Moreover, there was no statistically significant between p53 gene was found in Parkinson Disease. Conclusions: Understanding of the broad spectrum of clinical manifestations of Parkinson Disease is essential to the proper diagnosis of the disease. Genetic mutations or variants, chromosomal abnormalities are potential biomarkers that may improve diagnosis and allow the identification of persons at risk and better treatment options. P 5.021. IDENTIFICATION AND VERIFICATION OF NOVEL FBXO7 INTERACTING PROTEINS Wim Mandemakers , Roy Masius , Michelle Minneboo , Dick Dekkers , Jeroen Demmers , Max Kros , Vincenzo Bonifati . 1 Erasmus MC, Dept. of Clinial Genetics, Rotterdam, Netherlands; 2 Erasmus MC, Proteomics Center, Rotterdam, Netherlands; 3 Easmus MC, Dept. of Patholgy, Rotterdam, Netherlands Objectives: Parkinson disease-15 (PARK15), or parkinsonian-pyramidal syndrome, is caused by mutations in the FBXO7 gene. Although FBXO7 function is implicated in various cellular processes (i.e. cell cycle regulation and mitophagy), mechanistic insight into FBXO7 signaling pathways and consequences of PARK15 mutations is limited. The goal of our study is identification of novel FBXO7 interacting proteins and investigate the effect of PARK15 mutations on the detected interactions and related cellular processes. Methods: TAP-tag and GST-tag proteins of wildtype and mutated (R378G) FBXO7 were generated. DNA expression constructs of TAP-tagged FBXO7 proteins were transfected into human neuroblastoma cell lines (SH-SY5Y) and FBXO7 interacting protein were isolated by sequential pull down using FLAG and Streptactin peptide coated beads. GST-tagged proteins were used to pull down FBXO7 protein interactors from brain extracts. Various experimental paradigms were tested (i.e. investigation of cytoplasmic vs. nuclear interaction, phosphorylation dependent interactions, mitophagy dependent interactions). After pull down, eluates were fractionated by PAGE, Coomassie stained and processed for Mass Spec analysis. Candidate interactors were further validated in relevant follow up experiments. Results: Several FBXO7 protein interaction networks have been identified. Our data confirm previously identified interactions of FBXO7 with proteins from the SCF E3 ubiquitin ligase complex (CUL1, SKP1) and proteasome (PSMF1). In addition, novel FBXO7 interacting proteins involved in various functional pathways (i.e. mitochondrial and nuclear function) have been identified and are currently validated. Conclusions: Identification of novel FBXO7 protein interactors implicates SCF complex-dependent and -independent roles for FBXO7 function in various subcellular compartments (i.e. nucleus, mitochondria, cytoplasm). P 5.022. DEFECTIVE GLUCOCEREBROSIDASE IN GBA1 MUTANT PARKINSON'S DISEASE FIBROBLASTS IS RESCUED BY CHEMICAL CHAPERONE AMBROXOL THROUGH MODULATION OF LYSOSOMAL FACTORS