CLINICAL AND MOLECULAR CHARACTERIZATION AND GENOTYPE-PHENOTYPE CORRELATIONS OF PARKINSON'S DISEASE PATIENTS

Aim of the project: This research project aimed to integrate clinical and genetic data with the purpose of defining phenotype-genotype correlations and identifying different PD endo-phenotypes to create the settings for an effective diagnostic and therapeutic stratification of PD patients. Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder and is clinically characterized by the presence of motor (bradykinesia, rigidity, rest tremor and postural instability) and non-motor symptoms (cognitive impairment, autonomic dysfunction, sleep disorders, depression and hyposmia). The aetiology of PD is unknown except for a small but significant contribution of monogenic forms. Results: Harmonization of the genetic report for PD and improvement in the analysis of GBA1 gene by long read NGS technique improve and align the diagnostic of monogenic PD in Italy. The data on Ligurian PD population studied during the Ph D Course are aligned to literature data. Sixteen percent of the PD patients studied had a monogenic PD and 83% of them had a pathogenic variant in GBA1 gene. Moreover, one patient has been identified as a carrier of a variant in a new PD-associated gene: RAB32. Conclusion: the genetic studied of PD should be implemented in routine diagnostic test for all the patients. This is still not possible for the high cost of genetic testing and the availability of the techniques needed to have a complete and precise result. However, the implementation of genetic studying is crucial for precise medicine and for the implication that genetic information starting to have for the patients (from a prognostic and therapeutic point of view) and for their families.