Parkinson Disease
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTtargeted resequencing
The investigators will use a disease-specific gene panel including about 100 genes related to Parkinson's Disease, autophagy and levodopa induced Dyskinesia (LID).
Sponsors
Neuromed IRCCS
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| clinical evaluation of PD patients and controls | three years | disease progression (Hoehn and Yahr stadium, MDS-UPDRS part III, MoCA test, no motor symptoms, therapy and LID occurrence |
| identification of variants/mutations | two years | assessing if the inheritance of multiple rare deleterious variants in PD genes is predictive of PD risk. |
| association with phenotypic manifestation of PD | three years | The presence of one or more variants will be tested for association with phenotypic manifestation of PD (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. |
Countries
Italy
Contacts
Primary ContactTeresa Esposito, PhD
Outcome results
None listed