Hereditary Parkinson s Disease Natural History Protocol
Condition: Parkinson Disease 6, Early-Onset; Parkinson Disease (Autosomal Recessive, Early Onset) 7, Human; Parkinson Disease Autosomal Recessive, Early Onset; Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/Dj1
MeSH terms: Parkinson Disease; Parkinsonian Disorders
Study type: Observational

Summary: 
      Background:

      - Parkinson s disease is a disease of the nervous system that affects movement. People
      usually get it in their 70s or 80s. Early onset Parkinson s disease (EOPD) begins before the
      age of 50. Researchers think EOPD may be caused by a mutation in a gene. They want to study
      the genetic causes so they can find therapies for this disease.

      Objective:

      - To better understand the genetic causes of EOPD.

      Eligibility:

        -  Adults ages 18 80 with a history of EOPD. Their family members, who do not have
           Parkinson s disease, can join as controls.

        -  Healthy volunteers ages 18 80.

      Design:

        -  Participants with EOPD and their relatives will be screened with a review of medical
           records. Healthy volunteers will have medical history, physical exam, and blood drawn.

        -  Relatives may send blood samples to NIH to test for mutations in genes that are linked
           to Parkinson s disease. They may have a physical exam.

        -  Participants may be asked to return to clinic for another visit that can last up to 2
           hours.

        -  During this visit, participants will have blood taken from a vein in the arm via a
           needle stick.

        -  Participants may give a sample of their skin. The skin on the arm or leg will be numbed
           and a small skin punch biopsy will be taken with a special needle.

        -  Some cells from the blood or skin sample may be grown in a lab to establish cell lines.
           The cells may also potentially be genetically modified to make stem cells.

        -  Researchers may perform genetic analysis on the samples to compare them to EOPD patient
           samples.
    

Detailed description: 
      The majority of subjects with the degenerative Parkinson's Disease (PD) present in the 7th
      and 8th decades of life. In contrast, this neurologic disease can present within the first 5
      decades of life. This early onset presentation is more likely to have a direct genetic cause
      relative to the etiology of the degenerative form of the disease. Our understanding of the
      genetic causes of early onset Parkinson's Disease (EOPD) may help us find therapies for both
      the genetic and degenerative illnesses. Data from our laboratory and others show that genetic
      mutations associated with EOPD, disrupt cellular stress-response programs. These
      perturbations, in turn, impair cell-repair process, which is hypothesized to increase
      susceptibility to dopaminergic neuron degeneration linked to EOPD and degenerative PD. At the
      same time, patients with EOPD have a variable age of onset (spanning from 8 years to 41 years
      in the subjects in our cohort) and disease penetrance (severity of symptoms). The hypothesis
      we propose to test is whether the number and allele distributions of EOPD susceptibility gene
      mutations account for the variable age of onset and disease penetrance. This hypothesis will
      be tested in this natural history protocol by genotyping subjects with EOPD to define their
      genetic defects and to explore the cellular reparative function in these individuals using
      peripheral blood cells, skin biopsy derived fibroblasts and induced pluripotential stems
      cells derived from these subjects. In parallel, the phenotype of these subjects will be
      evaluated by the NINDS Parkinson's Clinic. Together, these data should advance our insight
      into the genotype-phenotype in EOPD pathophysiology.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Subjects that develop symptoms of Parkinson Disease within the first 5 decades of life
        would be enrolled onto this protocol. Additionally, subjects previously enrolled on
        protocol 12-H-0084 may also be enrolled on this protocol. Age (+/- 5 yrs) and gender
        matched healthy volunteers will be recruited as controls for this protocol. Controls will
        be recruited via web advertisements. An email advertisement will also be sent out via the
        NIH LISTSERV to aid in the recruitment of healthy volunteers. A list of healthy volunteers
        may also be requested from the NIH Office of Patient Recruitment. Family member controls
        without clinical evidence of Parkinsonism may be recruited as controls for index research
        subjects.
      
Keywords: Early Onset Parkinson's Disease; Cellular Quality Control Programs; Mitochondria; Neuroinflammation; Immunology; Natural History