Phenotypic Spectrum of SNCA G209A Mutation Carriers for Familial Parkinson's Disease in Greece (P2.022)

Objective: To characterize the phenotype of SNCA G209A mutation carriers in familial PD Background: The G209A mutation in the SNCA gene encoding for alpha-synuclein was the first Mendelian genetic defect identified in Parkinson9s Disease (Polymeropoulos et al., 1997). The mutation occurred in families of Italian and Greek origin with an autosomal dominant pattern of inheritance. Design: Currently, as part of the FP7 Project MEFOPA (http://www.mefopa.eu/), we are attempting to identify living carriers of the G209A SNCA mutation in Greece. We are registering demographic and clinical information, performing relevant questionnaires and scales, as well as obtaining biological samples in order to establish in a more systematic fashion the clinical spectrum of the phenotype of the disease, and to examine questions regarding its biological underpinnings. Results: We have so far registered 30 mutation carriers and we have followed them for at least two years. Of the 30 carriers, 8 are asymptomatic. Seven probands belong to new families, apparently unrelated to those already known to carry the G209A SNCA mutation. Mean age of disease onset is 44.8+/- 10.3 years (range 30-65), and mean disease duration is 7.1+/-4.3 years (range 0.5-18). There is a large variability in the clinical phenotype ranging from a still asymptomatic carrier at age 90 to subjects presenting with early disease onset and either a relatively benign clinical course or rapid progression to dementia. There is also a varied range of presentation of Non-Motor symptoms such as depression, psychosis and dementia. Conclusion: G209A SNCA carriers demonstrate a wide clinical phenotypic spectrum. The presence of the G209A SNCA mutation in subjects from unidentified families underscores the utility of screening for this mutation in Greek PD patients with a compatible inheritance pattern. The biggest challenge now is to identify the biological basis of this variability providing a foundation for novel therapeutics. Disclosure: Dr. Papadimitriou has nothing to disclose. Dr. Antonelou has nothing to disclose. Dr. Bozi has nothing to disclose. Dr. Maniati has nothing to disclose. Dr. Papagiannakis has nothing to disclose. Dr. Bostantjopoulou has nothing to disclose. Dr. Leonardos has nothing to disclose. Dr. Papageorgiou has nothing to disclose. Dr. Hadjigeorgiou has nothing to disclose. Dr. Kapaki has nothing to disclose. Dr. Tagaris has nothing to disclose. Dr. Papadimitriou has nothing to disclose. Dr. Athanassiadou has nothing to disclose. Dr. Stefanis has nothing to disclose.