What is Genetic Research?
Unfortunately we have not yet identified all the genes that cause inherited movement disorders and there are many movement disorders for which a genetic test is not yet available. We need to continue our efforts working with families affected with inherited movement disorders to discover new genes and develop new tests. Most genetic research efforts involve the participation of affected individuals and, if applicable (and available), their affected or unaffected family members. Study participation typically requires a single visit of approximately one hour, and usually involves a blood draw (for DNA analysis), a neurological exam, questionnaires on family and medical history and video-taping. All genetic research at Columbia University is approved by the institutional review board (IRB) and requires the reading and signing of consent forms. (The IRB is a committee organized to protect the rights and welfare of human subjects involved in research).
There are major differences between clinical genetic testing and genetic research. These are summarized in the table below:
|Clinical Genetic Testing||Genetic Research|
|Gene being testing is well understood||Gene being researched is not well understood|
|Results are used for clinical purposes||Results are not used for clinical purposes|
|Results given to patient||Results not intended for patient use|
|Clinical testing laboratory is government regulated||Research testing laboratory is not government regulated|
|Patient signs a clinical consent form||Patient signs a research consent form|
|Patient / insurance covers cost of clinical test||There is no cost to patient for genetic research|
|Insurance companies covering test can access results if audited||Insurance companies do not access and cannot use research results|
|Both testing and research are voluntary procedures and should be discussed at length with physician/genetic counselor|
Table 3. Differences and similarities between clinical genetic testing and genetic research
The Division of Movement Disorders is involved in the following on-site research:
- Parkinson's disease: Inheritance of Parkinson's disease (PD) for most individuals with PD is complex, involving multiple genetic and environmental factors. The Division of Movement Disorders has focused on genetic research involving young-onset PD.
We are currently collaborating with principle investigator Karen Marder, MD, MPH. (Sergievsky Center and Taub Institute, Columbia University, New York) and laboratory director, Lorraine N. Clark, PhD. (Taub Institute, Columbia University, New York) in a major NIH-funded, multi-site, young-onset genetic PD study.
We are also collaborating directly with Lorraine Clark, PhD at Columbia University, in studies to identify whether specific presentations of Parkinson's disease can be correlated with specific genes and mutations. Using state of the art technology including gene chips, Dr Clark is developing new and innovative ways to identify the genetic factors that may lead to the development of Parkinson's disease.
For more information about young-onset PD genetic research (onset of motor symptoms at age 50 years or less) call Helen Mejia Santana on (212) 305-9183. If you have PD and have a sibling who is alive and also has PD (neither of you need live in New York), please contact Jill Goldman at (212) 305-4473. If you have PD and all four of your grandparents are of Ashkenazi Jewish ancestry, you may be eligible for a new study looking at risk factors for PD in this population. Please contact Jill Goldman at (212) 305-4473.
- Essential tremor (ET): ET is the most common form of tremor. There are familial and non-familial forms of ET and a number of autosomal dominant families have been described. Dr. Elan Louis is directing ET research efforts at the Division of Movement Disorders. If you are interested in participating in ET research studies and you are 18 years or older, please contact Eileen Rios at (212) 305-8601.
The Division of Movement Disorders is also collaborating with outside sites on a number of studies listed below. To participate in the research below, you must already be a patient at the Division of Movement Disorders. A brief summary of the research for each condition is given.
- Ataxia: Ataxia is a form of incoordination that can occur as part of a constellation of symptoms caused by neurodegeneration of the cerebellar. It can also be part of a syndrome. There are genetic (familial) and non-genetic forms of ataxia. Over 10 genes associated with ataxia have already been identified. There are many forms of familial ataxia for which the genetics is not yet understood.
- Chorea: There are a number of genetic diseases, which have chorea (involuntary movements of the head, trunk and limbs) as a component. Although we know the genetic cause of Huntington disease and Huntington disease-Like 2, there are other similar familial diseases for which we do not yet understand the genetic basis.
- Dystonia: Dystonia refers to twisting movements that are frequently repetitive, and often progress to prolonged abnormal postures. The genetic basis of one form of early-onset torsion dystonia (DYT1), dopa-responsive dystonia and myoclonus dystonia is known. However we do not yet understand the genetics of other forms of familial dystonias. The adult-onset focal dystonias (for example dystonia affecting the neck or eyes) are thought to be caused by a combination of genetic and non-genetic factors. Researchers are looking for these genetic factors.
- Paroxysmal Dyskinesias: These movements are characterized by transient symptoms of varying frequency, severity, duration and aggravating factors. They can be induced by movement or by factors other than movement (such as caffeine or stress). Most familial forms of the paroxysmal dyskinesias are autosomal dominant. A number of sites on chromosomes 1, 2 and 16 are thought to contain genes that cause this group of disorders.
- Tourette Syndrome (TS): TS is characterized by motor and phonic tics and behavioral symptoms. TS is usually familial and is often accompanied by attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD) and other behavioral problems. Researchers are trying to find the genes that cause TS.
Please contact Jill Goldman at (212) 305-4473 for more information about our collaborative research efforts for ataxia, chorea, dystonia, paroxysmal dyskinesia and Tourette syndrome.
Research publications, letters and abstracts published by faculty at the Division of Movement Disorders have resulted from collaborations with Karen Marder, MD, and MPH (Sergievsky Center and Taub Institute, Columbia University, New York), Lorraine N. Clark, PhD (Taub Institute, Columbia University, New York), Christine Klein, MD (Luebeck University, Germany), Russell L. Margolis, MD (Johns Hopkins University School of Medicine, Maryland), Susan Bressman, MD (Beth Israel Medical Center, New York) and Laurie Ozelius, PhD., (Albert Einstein College of Medicine, New York)
- Clark, L, Afridi, S., Mejia-Santana, H, Harris, J., Louis, E., Cote, L., Andrews, H., Singleton, A., Wavrant De-Vrieze, F., Hardy, J., Mayeux, R., Fahn, S., Waters, C., Ford, B., Frucht, S., Ottman, R., Marder, K. Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations. Movement Disorders:7:796-800 (2004).
- Clark LN, Nicolai A, Afridi S, Harris J, Mejia-Santana H, Strug L, Cote LJ, Louis ED, Andrews H, Waters C, Ford B, Frucht S, Fahn S, Mayeux R, Ottman R, Marder K. Pilot association study of the beta-glucocerebrosidase N370S allele and Parkinson's disease in subjects of Jewish ethnicity. Mov Disord. 2005 Jan;20(1):100-3.
- Hedrich, K., Marder, K., Harris, J.,Kann, M., Lynch, T., Meija-Santana H., Pramstaller, P., Schwinger, E., Bressman, S., Fahn, S., Klein, C.,. Evaluation of 50 Probands with Early-Onset Parkinson's Disease for Parkin Mutations. Neurology. 23;58(8):1239-46. (2002).
- Klein., C, Schilling K., Saunders-Pullman, R.J., Garrels J., Breakefield, XO., Brin, M.F., deLeon D., Doheny D., Fahn S., Fink, J.S., Forsgren, L., Friedman, J., Frucht, S., Harris, J., Holmgren, G., Kis, B., Kurlan R., Kyllerman, M., Lang, A.E., Leung, J., Raymond, D., Robishaw, J.D., Sanner, G., Schwinger, E., Tabamo, R.E., Tagliati, M. A Major Locus for Myoclonus-dystonia Maps to Chromosome 7q in Eight Families. American Journal of Human Genetics. 67(5), 1314-9 (2000).
- Levy, G., Louis, E., Cote, L., Perez, M., Mejia-Santana, H., Andrews, H., Harris, J., Waters, C., Ford, B., Frucht, S., Fahn, S., Marder, K., Contribution of Aging to the Severity of Different Motor Signs in Parkinson's Disease. Archives of Neurology 2005 Mar;62(3):467-72.
- Levy, G, Louis, E., Mejia-Santana, H., Cote, L., Andrews, Howard, Harris, Juliette, Waters, Cheryl, Ford, B., Frucht, S., Fahn, S., Ottman, R., Marder, K. Lack of Familial Aggregation of Parkinson Disease and Alzheimer Disease. Archives of Neurology: 61:1033-1039 (2004).
- Louis, E., Levy, G., Mejia-Santana, H., Cote, L., Andrews, H., Harris, J., Waters, C., Ford, B., Frucht, S., Fahn, S., Ottman, R., Marder, K. Risk of Action Tremor in Relatives of Tremor Dominant and Postural Instability Gait Disorder PD. Neurology: 14;61(7):931-936 (2003).
- Marder, K., Levy, G., Louis, E., Mejia-Santana, H., Cote, L., Andrews, H., Harris, J., Waters, C., Ford, B., Frucht, S., Fahn, S., Ottman, R. Accuracy of Family History Data on Parkinson's Disease. Neurology; 61: 18-23 (2003).
- Marder, K, Levy, G., Louis, E.D., Mejia-Santana, H., Cote, L., Andrews, H., Harris, J., Waters, C., Ford, B., Frucht, S., Fahn, S., Ottman, R. Familial Aggregation of Early and Late-Onset PD. Annals of Neurology: 54:507-513 (2003)
- Margolis, R., Holmes, S., Rosenblatt, A., Gourley, L., O'Hearn, E., Ross, C., Seltzer, W., Walker, R., Ashizawa, T., Rasmussen, A., Hayden, M., Almqvist, E., Harris, J., Fahn, S., MacDonald, M., Mysore, J., Shimohata, T., Tsuji, S., Potter, N., Nakaso, K., Adachi, Y., Nakashima, K., Bird, T., Krause, A., Greenstein, A., Huntington's Disease-like 2 (HDL2) in North America and Japan. Annals of Neurology 2004 Nov;56(5):670-4. Erratum in: Ann Neurol. 2004 Dec;56 (6):911
- Harris, J and Fahn, S. Movement Disorders. The Molecular and Genetic Basis of Neurologic and Psychiatric Disease 3rd Edition (RN Rosenberg, S. Prusiner, S. DiMauro, R.L. Barchi, E.J. Nestler). Butterworth & Heinemann: MA. (September, 2003).
- Kann M, Hedrich K, Vieregge P, Jacobs H, Muller B, Kock N, Schwinger E, Klein C, Marder K, Harris J, Meija-Santana H, Bressman S, Ozelius LJ, Lang AE, Pramstaller PP. The Parkin Gene is Not Involved in Late-onset Parkinson's disease. Neurology 2;58(5):835. (2002).
- Kock, N., Müller, B., Vieregge, P., Pramstaller, P., Marder, K., Abbruzzese, G., Martinelli, P., Lang, A., Jacobs, H., Hagenah, J., Harris, J., Meija-Santana, H., Fahn, S., Hedrich, K., Kann, M., Gehlken, U., Culjkovic, PB., Schwinger, E., Wszolek, Z., Zühlke, C., Klein, C. Role of SCA-2 Mutations in Early- and Late-onset Dopa-responsive Parkinsonism. Ann. Neurol; 52(2); 257-8. (2002).
- Klein, C., Hedrich, K., Wellenbrock, C., Kann, M., Harris, J., Marder, K., Lang, A.E., Schwinger, E., Ozelius, L.J., Vieregge, P., Pramstaller, P.P., Kramer, P.L. Frequency of Parkin Mutations in Late-onset Parkinson's Disease. Ann. Neurol: 54 (3):415-6 (2003).
- Chatterjee A, Levy G, Louis E, Mejia-Santana H, Cote L, Andrews H, Harris J, Waters C, Ford B, Frucht S, Fahn S, Ottman R ,Marder K. Apathy and Psychosis in early vs. late onset Parkinson disease. Annals of Neurology (2004)
- Clark, L.N., Singleton, A., Harris, J., Mejia, H., Cote, L.J., Louis, E.D., Hardy, J., Marder, K. Frequency of mutations in the DJ1 gene in an early-onset multi-ethnic Parkinson's disease cohort. Alzheimer's and Parkinson's Diseases: New Perspectives. 6th International Conference. AD/PD (2003)
- Clark LN, Nicolai A, Harris J, Mejia-Santana H, Cote LJ, Louis ED, Fahn S and Marder K. Frequency of the Glucocerebrosidase N370S mutation and Susceptibilty to Parkinson's Disease in a cohort of Ashkenazi Jewish Ethnicity. 2003;S73:1999. The American Journal of Human Genetics. S73:(2004)
- Harris J, Afridi S, Greene P, Fahn S, Marder K, Clark LN. (2003) Parkin Mutations Cause Late-Onset Slowly Progressing Parkinson's Disease. The American Journal of Human Genetics. S73 (2003)
- Hedrich K., Eskelson C., Marder K., Harris J., Meija-Santana H., Vieregge P., Jacobs H., Bressman S.B., Lang A.E., Wang S., Kann M., Schwinger E., Ozelius L.J., Pramstaller P.P., Kramer P.L., Klein C. Recurrent mutations in the parkin gene. Poster: The Society for Neuroscience (2002)
- Hedrich, K., Klein, C., Harris, J., Kann, M., Lynch, T., Santana, H., Schwinger, E., Pramstaller, P.P., Bolzano, M.D., Vieregge, P., Bressman, S., Fahn, S., Marder, K. Evaluation of a large patient cohort with Early-Onset Parkinson's Disease for mutations in the Parkin gene. Poster: The 53rd Annual Meeting of the American Academy of Neurology, (2001).
- Hedrich K, Klein C, Harris J, Marder K. Evaluation of a large patient cohort with early-onset Parkinson's disease for mutations in the Parkin gene. Neurology 56 (suppl 3) A224 (2001).
- Liu, L., de Carvalho Aguiar, P., Kock, N., Mueller, B., Raymond, D., Harris, J., Doheny, D., Frucht, S., Ford, B., Lynch, T., deLeon, D., Garrels, J., Schwinger, E., Brin, M., Kurlan, R., Lang, A., Fahn, S., Saunders-Pullman, R., Borges, V., Ferraz, H.B., Friedman, J., Klein, C., Bressman, S., Ozelius, L. Mutational Analysis and Identification of Differential Methylation Patterns in the SGCE Gene in Patients with Myoclonus Dystonia. Poster: The 52nd Annual Meeting of the American Society of Human Genetics, (2002).
- Marder K, Levy G, Louis E, Mejia-Santana H, Harris J, Waters C, Greene P, Ford B, Frucht S, Andrews H, Fahn S, Ottman R. Clinical phenotypes associated with a genetic susceptibility to PD. Neurology 60: A437,(2003)
- Ozelius, L., Liu, L., Kock, N., de Carvalho Aguiar, P., Mueller, B., Raymond, D., Harris, J., Doheny, D., Frucht, S., Ford, B., Lynch, T., deLeon, D., Garrels, J., Schwinger, E., Brin, M., Kurlan, R., Lang, A., Fahn, S., Saunders-Pullman, R., Klein, C., Bressman, S. Mutation Analysis of the Epsilon-Sarcoglycan (SGCE) Gene in Ten Families with Myoclonus-Dystonia. Poster: The 54th Annual Meeting of the American Academy of Neurology, (2002).