Genetic Characterization of Parkinson's Disease
Genetic Characterization of Parkinson's Disease
This study will explore the risks and causes of Parkinson's disease, a chronic progressive
 nervous system disorder. Patients typically have tremors, muscle weakness and a shuffling
 gait.

 Patients with Parkinson's disease, their relatives and healthy volunteers may be eligible for
 this study. Candidates must be 18 years of age or older. Patients whose parkinsonism is due
 to a secondary cause, such as infection or injury, and healthy volunteers who have a first
 degree family member (parent, grandparent, child, sibling) with Parkinson's disease are
 excluded from enrollment.

 Participants are asked about possible symptoms they may have and about their general health.
 They provide a blood sample to obtain DNA for genetic analysis to look for genetic
 differences that might be related to risks for Parkinson's disease. White blood cells may be
 treated in the laboratory to grow a cell line, which provides a source of substances in the
 blood without having to draw samples repeatedly.
Parkinson's disease (PD) was noted to have a familial component as early as 1880. More
 recently, the discovery of several genetic factors influencing Parkinson's disease has
 emphasized the importance of heredity in PD.

 Objective: The goal of this protocol will be to contribute to the genetic understanding of
 Parkinson's disease. Clinical data will be collected in order to document the features of
 Parkinson's disease in affected individuals (phenotyping). Genetic characterization will be
 undertaken for the discovery of specific genes which cause or contribute to the risk for
 Parkinson's disease (genotyping).

 Design: The study design has two components. The first (aim 1) involves positional cloning
 for gene discovery in families with apparent Mendelian inheritance. The second (aim 2) will
 utilize an association study design, using genetic case-control methods for assessment of
 genetic risk factors. We will examine individuals affected by Parkinson's disease and their
 family members towards Specific Aim 1. Specific Aim 2 will involve evaluation of individuals
 with apparent sporadic Parkinson's disease, and also, healthy adult volunteers who will be
 recruited as control subjects.

 Outcome Measures:

 Primary Outcome Measures for Specific Aim 1 are:

 1. The identification of new genes causal for Parkinson's disease.

 2. The identification of new mutations in known genes.

 Primary Outcome Measures for Specific Aim 2 are:

 1. The discovery of gene variants which confer risk for Parkinson's disease.

 2. The validation of already reported polymorphisms as risk factors for PD.

 Secondary Outcome Measures (both Specific Aims 1 and 2): Genotype/phenotype correlations for
 specific genetic forms of Parkinson's disease. For example, we will assess if a particular
 age of onset, cardinal or secondary feature of PD or associated clinical course is associated
 with a given genotype.

 Future Direction: Because 1) the larger sample base the greater the likelihood of the
 discovery of genes of minor effect and 2) discoveries of genetic risk factors require
 validation in additional sample series, it is likely that renewal of this protocol will be
 sought after five years.

 Study Population: We aim to enroll a total of 2500 subjects over five years. These will
 include approximately 500 samples for the Mendelian studies (Specific Aim 1), and 2000 for
 association studies (Specific Aim 2). These estimates are based both on feasibility and on
 statistical power. Subjects will be evaluated at the NIH Clinical Center.
INCLUSION CRITERIA:

 Individuals with Parkinson's disease OR

 Family members of an individual diagnosed with Parkinson's disease OR

 Healthy adult controls obtained through the NIH Clinical Research Volunteers Program (CVRP)
 or other healthy control volunteers who come forward.

 EXCLUSION CRITERIA:

 Under the age of 18 years of age OR

 Individuals with Parkinsonism secondary to a specific cause such as toxin exposure, birth
 injury, head injury, or brain infection such as encephalitis.

 Healthy volunteers with a medical history or first degree family history of Parkinson's
 disease.