Phenotype/Genotype Correlations in Movement Disorders

Обзор

The goal of this protocol is to identify families with inherited movement disorders and evaluate disease manifestations to establish an accurate clinical diagnosis by using newest technological advances and investigate the underlying molecular mechanisms. Studies of inherited movement disorders in large families with good genealogical records are especially valuable. Patients with diseases of known molecular basis will be genotyped in order to investigate phenotype/genotype correlation. Patients with disease of unknown or incomplete genetic characterization will be studied with a hope of contributing to the identification of specific disease-causing genes and genetic mechanisms responsible for a specific disorder.

Подробное описание

Objective: The primary objective of this study is to perform phenotypic and genotypic characterizations of patients and family members with a known or suspected diagnosis of a movement disorder and screen for eligibility to participate in other movement disorder related protocols:

* 14-N-0086 Deep brain stimulation therapy in movement disorders * 11-N-0211 Deep brain stimulation surgery for movement disorders * 000865: Natural history of movement disorders * 00-N-0043: Clinical and molecular manifestations of inherited neurologic disorders * 03-AG-N-329 (NIA): The genetic characterization of movement disorders and dementias * 20M0082 Phase 1 Study: PET Imaging of Cyclooxygenases in Neurodegenerative Brain Disease; Institute (NIMH)

The secondary goals of this protocol are to learn more about genetic causes of movement disorders and their phenotypic associations; identify patients and families with inherited movement disorders; evaluate disease manifestations to establish an accurate clinical diagnosis; and to investigate the underlying molecular mechanisms. Studies of inherited movement disorders in large families with well-documented genealogical records are especially valuable. The study will also assess a series of exploratory peripheral biomarkers, including, but not limited to, those delineated by DNA, RNA, protein, and/or metabolite alterations in an effort to more accurately predict those with, or at risk of having, the specific neurological disease.

Study population: Subjects older than 2 years old with movement disorders and their family members will be enrolled. Patients with diseases of known molecular basis will be genotyped in order to investigate phenotype/genotype correlations. Patients with disease of unknown or incomplete genetic characterization will be studied with a hope of contributing to the identification of specific disease-causing genes and genetic mechanisms and/or peripheral bio-signatures involved in a particular disorder.

Design:

This is an observational diagnostic study of movement disorders and their progression and pathophysiology.

Outcome measures: Determination of phenotype/genotype correlations in specific movement disorders, referral of patients and/or family members for participation in other NIH studies, gene identification if not known, gene expression and protein, metabolite and nucleic acid levels, collection of blood cells and generation of induced pluripotent stem cell lines, and establishment of a clinical diagnosis when possible.

Первичные конечные точки

• The primary outcome measure is the phenotypic and genotypic characterizations of patients and family members with movement disorders. [Срок оценки: 10 Years]

Вторичные конечные точки (5)

• Identification of disease-specific biomarkers in stem cells derived from patient peripheral blood mononuclear cells or fibroblast lines [Срок оценки: Study end]
• Identification of new genes and/or peripheral blood biomarkers associated with movement disorders [Срок оценки: Study end]
• Identification of new genes and/or peripheral blood biomarkers associated with movement disorders. [Срок оценки: Study end]
• Establishment of a clinical diagnosis (when possible) [Срок оценки: Study end]
• Referral of patients and/or family members for participation in other NIH studies [Срок оценки: Study end]

Критерии участия

• INCLUSION CRITERIA:
• Individuals with suspected movement disorders
• Family members of movement disorders patients
• Ability to give informed consent or have a legally authorized representative able to give consent (for adults without consent capacity) or parent/guardian able to provide informed consent (for a child)
• If unable to give informed consent, ability to give assent (for children or adults without consent capacity)
• NIH Employees can participate in this study if they meet eligibility.

Критерии исключения

• Pregnant women
• Children less than 2 years of age
• Employees of the Parkinson's Disease Clinic, NINDS

Exclusion criteria for MRI

• Presence of metal in subject s body which would make having an MRI scan unsafe, such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants or shrapnel fragments, or if subject was a welder or metal worker, since small metal fragments in the eye may be present.
• Subject is uncomfortable in small closed spaces (have claustrophobia) so that they would feel uncomfortable in the MRI machine.
• Unable to lie comfortably on back for up to 1 hour
• Under 12 years of age

There is no general exclusion for NIH employees.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Только случаи

Центры проведения

США · 1 центр

• National Institutes of Health Clinical Center — Bethesda

Публикации

• Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A PMID 11181995
• Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann Y, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R PMID 11237011
• Stolerman ES, Florez JC. Genomics of type 2 diabetes mellitus: implications for the clinician. Nat Rev Endocrinol. 2009 Aug;5(8):429-36. doi: 10.1038/nrendo.2009.129. Epub 2009 Jun 30. PMID 19564886

Идентификаторы

NCT: NCT00018889 · 010206 · 01-N-0206

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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