IDENTIFICATION OF A NOVEL GENE FOR AUTOSOMAL RECESSIVE EARLY-ONSET PARKINSONISM (PARK6) AND GENOTYPE-PHENOTYPE CORRELATION

This project aims to identify and characterize a novel gene (PARK6) responsible for autosomal recessive juvenile parkinsonism (ARJP). To date, only one ARJP gene (Parkin on chromosome 6) has been cloned. We have mapped a second ARJP locus (PARK6) in 4 European families. A third locus (PARK7) has been recently identified by the Neurogenetic Group at the Erasmus University (Rotterdam). This study will be carried on in collaboration with the Italian Consortium for clinical and genetic study of parkinsonisms, the European Consortium on Genetic Susceptibility in PD and other Italian and European centers. The Italian Consortium has been created over the last year, through the effort of 6 movement disorders units with a long-standing experience in diagnosis and therapy of movement disorders. The European Consortium groups several European countries (see Notes). These collaborations will allow the applicant to collect a broad sample of sporadic and familial (autosomal recessive) cases affected by early-onset parkinsonism. This study will pursue the following objectives: (1) screening of candidate genes within the PARK6 region, to identify the responsible gene (two suitable genes have been selected); (2) collection and characterization of familial and sporadic cases with early-onset parkinsonism; (3) evaluation of PARK6 prevalence in Italy and Europe, detection of founder mutations and identification of genotype-phenotype correlates. This project is focused on PARK6 only. Families showing linkage to PARK7 will be shared with the Neurogenetic group at the Erasmus University, while families showing linkage to PARK2 will be sent to the Besta Hospital for molecular analysis of the Parkin gene. Research on genetic causes of early onset parkinsonism will allow to better understand the pathogenetic process of a frequent, high-morbidity disease such as Parkinson's Disease, improving diagnostic and therapeutic approaches and genetic counselling.