Assessing the Polygenic Burden of Rare Disruptive Mutations in Parkinson's Disease
Assessing the Polygenic Burden of Rare Disruptive Mutations in Parkinson's Disease
The project intends to assess the polygenic burden of rare disruptive mutations in
 Parkinson's disease (PD) and how they influence the phenotype/pathological heterogeneity of
 disease.
The investigators intend to extend the genetic analysis to a cohort of 300 PD cases and 300
 healthy subjects (wife / husband of the patients) that will be recruited at Scientific
 Institute for Research, Hospitalization and Healthcare (IRCCS) Neuromed.

 After signed informed consent patients will be assessed for disease progression (Hoehn and
 Yahr stadium, Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III
 (MDS-UPDRS), Montreal Cognitive Assessment (MoCA) test, no motor symptoms, therapy and
 levodopa induced Dyskinesia (LID) occurrence). Each patient and control will be subjected to
 peripheral blood sampling for the isolation of DNA, RNA, plasma and serum. The investigators
 will use a disease-specific gene panel including about 100 genes related to Parkinson's
 Disease, autophagy and levodopa induced Dyskinesia (LID).

 Bioinformatics analysis will allow to catalog in a database the identified variants/mutations
 according to their frequency and characteristics.

 The investigators will specifically assess if the inheritance of multiple rare deleterious
 variants in Parkinson's Disease genes is predictive of disease risk.

 The presence of one or more variants will be tested for association with phenotypic
 manifestation of Parkinson's Disease (motor, non-motor, and cognitive signs, as well as age
 at onset, LID and neuroimaging changes) to assess the variant burden effect on progression,
 and prognosis of the disease.
Inclusion Criteria:

 -  Presence of at least two out the following cardinal signs: resting tremor, cogwheel
 rigidity, bradykinesia, asymmetrical onset of symptoms and symptomatic response to
 L-dopa (levodopa).

 Exclusion Criteria:

 -  Previous thalamotomy on the implanted sides;

 -  Significant brain atrophy or structural damage seen on CT or MRI;

 -  Marked cognitive dysfunction;

 -  Active psychiatric symptoms;

 -  Concurrent neurological disorders;

 -  Other uncontrolled medical disorders.