Protective Genetic Factors Against Neurological Diseases

Study Overview
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Brief Summary
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NIH Precision Medicine Initiative, started in May 2018, will enroll one million people through an online portal. It hopes to identify genetic variants affecting a variety of human phenotypic outcomes. A giant set of data like this may enable an association of genetic variants with a certain phenotype. However, the association is often compromised due to the collection of phenotypic data that is not well controlled or standardized creating noisy data. These phenotypic noises can be largely eliminated in clinical studies with stringent criteria and standardization of outcome measurements. In this study, by looking mainly at genetic information and nerve conduction speed, we hope to eliminate the extra noises in the data set. Eliminating the extra noises should allow us to be able to determine if there are genetic differences between neurological disorders and healthy controls, and if these genetic differences can be attributed to the speed of the nerve conduction.

Official Title
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Protective Genetic Factors Against Neurological Diseases

Conditions
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Neurological Disorder, Healthy Control

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of a neurological disorder - Inherited Peripheral Neuropathy, Charcot Marie Tooth, Multiple Sclerosis, or Parkinson's Disease Healthy volunteers with no history of medical conditions known to afflict the nervous system will be recruited as normal controls. Age 18-100 (Inclusive) Able to undergo MRI Medically Stable Exclusion Criteria: Any subject unwilling to undergo genetic testing (DNA sampling) Any subjects with history of peripheral nerve diseases or conditions known to affect the CNS, such as diabetes, stroke, thyroid disease, chemotherapy, renal failure, etc. Note: This study holds no additional risk for pregnant women and they will not be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Neurological Disorder<br>For all neurological disorder participants an electromyography (EMG) study will be done to determine nerve conduction speed, and a blood draw will be completed for genetic (DNA) testing. Motor measures, cognitive measures and surveys will be completed to assess walking and brain processing speed. Four optional assessments will be offered and only completed if the participant consents to them and include: optical coherence tomography (pictures of the back of the eye), visual evoked potential (to evaluate the nerve pathways of the eye), brain MRI, and skin biopsy. For participants with a diagnosis of Charcot Marie Tooth (CMT) disease, they will have an additional Neuropathy Score to assess disease severity. | |
| Healthy Control<br>An electromyography (EMG) study will be done to determine nerve conduction speed, and a blood draw will be completed for genetic (DNA) testing. Motor measures, cognitive measures and surveys will be completed to assess walking and brain processing speed. Four optional assessments will be offered and only completed if the participant consents to them and include: optical coherence tomography (pictures of the back of the eye), visual evoked potential (to evaluate the nerve pathways of the eye), brain MRI, and skin biopsy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of human genetic variants with the fastest conduction speed in normal controls | nerve conduction velocity as measured by electromyogram machine | 5 years | 
| The cluster of genetic variants associated with the fastest conduction velocity in normal controls versus those altered in patients with neurological diseases will be characterized | nerve conduction velocity and neurological disability scores as assessed by Visser Neuropathy Score ranging from 0-68 with higher score indicating more severe disabilities. | 5 years | 
| To test if the genetic variants associated with the fastest CV in the PNS protect some patients with CMT1A from developing severe disabilities | neurological disability scores as assessed by Visser Neuropathy Score ranging from 0-68 with higher score indicating more severe disabilities. | 5 years |