Background and purpose Although the first mutation associated with Parkinson's disease (PD) was identified several years ago in the alpha‐synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population. Methods A genetic analysis in 111 familial or sporadic with early‐onset (≤50 years, EO) PD patients was performed for the presence of the A53T SNCA mutation. In separate subgroups of these patients, further mutations in the SNCA, LRRK2, Parkin, PINK1 and DJ‐1 genes were searched for. Additionally, a subgroup of familial cases was analysed for mutations in the glucocerebrosidase (GBA) gene. Results In total, five patients (4.5% of our whole population) were identified with the A53T SNCA mutation, two with a heterozygote dosage mutation and one with a heterozygote point mutation in the Parkin gene, and seven patients (10.3% of our familial cohort) with GBA gene mutations. Conclusions The A53T mutation in the SNCA gene, although uncommon, does represent a cause of PD in the Greek population, especially of familial EOPD with autosomal dominant inheritance. GBA mutations in the familial cohort tested here were as common as in a cohort of sporadic cases previously examined from the same centres. For the remainder of the genes, genetic defects that could definitively account for the disease were not identified. These results suggest that further Mendelian traits that lead to PD in the Greek population remain to be identified.

We compared phenotypic characteristics in 35 Greek patients with Parkinson's disease (PD), carriers of GBA1 mutations (GBA-PD), with 35 Genetically Unidentified PD patients (GU-PD). We found a previously reported higher prevalence of cognitive impairment and a little appreciated more frequent bilateral onset of the disease in GBA-PD vs GU-PD. As far as the exposure to environmental factors, linked to PD, is concerned, our study hints to the possibility that pesticide exposure may be more common in GBA-PD patients, and possibly act synergistically with the mutation carrier status to trigger the disease.

Background: Variations of α-synuclein levels have been reported in serum and plasma in Parkinson's Disease (PD) Patients.Methods: Serum and plasma were obtained from PD patients without known mutations (GU-PD, n=124)), carriers of the A53T/G209A point mutation in the αsynuclein gene (SNCA) (n=29), and respective age-/sex-matched controls. Levels of total α-synuclein were assessed using an in-house ELISA assay.Results: A statistically significant increase of α-synuclein levels was found in serum, but not plasma, from GU-PD patients compared to healthy controls. A statistically significant decrease of α-synuclein levels was found in serum and plasma from symptomatic A53T mutation carriers compared to healthy controls. Plasma αsynuclein levels were modestly negatively correlated with UPDRS part III score and disease duration in A53T-PD patients. Conclusion:Increased α-synuclein levels in serum of GU-PD patients suggest a systemic deregulation of α-synuclein homeostasis in PD. The opposite results in A53T-PD highlight the complexity of α-synuclein homeostatic regulation in PD, and suggest the possibility of reduced expression of the mutant allele.

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