Parkin Mutations and Their Functional Consequences

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ClinicalTrials.gov Identifier: NCT00136721

Recruitment Status : Unknown

Verified December 2007 by Institut National de la Santé Et de la Recherche Médicale, France.
Recruitment status was: Active, not recruiting

First Posted : August 29, 2005

Last Update Posted : December 4, 2007

Sponsor:

Collaborator:

National Institutes of Health (NIH)

Information provided by:

Institut National de la Santé Et de la Recherche Médicale, France

Study Description

Brief Summary:

Parkinson's disease (PD) is the most frequent neurodegenerative disease with a prevalence of 2% over 65 years and because of this high prevalence as the population ages, it is a major problem of public health.

An exhaustive repertory of not only parkin mutations in autosomal recessive forms of PD but also in other known genes such as DJ-1, PINK1 and LRRK2, is of major importance for both genetic counseling in families affected with PD and physiopathological approaches to this disease.

Through a French network for the study of Parkinson's disease genetics and extended collaborations with European, Mediterranean and other various countries, a total of 2934 subjects including 1683 patients and 1251 unaffected individuals has been collected since 2002. These samples consisted of 122 families with autosomal recessive PD, 285 cases of isolated early onset PD, 110 autosomal recessive and 129 autosomal dominant families with late onset PD, 201 isolated late onset PD cases and 250 matched controls.

DNAs from all subjects are now available, lymphocytes and lymphoblastoid cell lines have been stored for most patients from France and recently, fresh fibroblasts have been obtained for some individuals.

The genetic approach to autosomal recessive PD is focused on the identification of mutations in the parkin gene but also on the screening of DJ-1, PINK1 and LRRK2 genes.

Condition or disease
Parkinson's Disease

Study Design

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Study Type :	Observational
Enrollment :	2500 participants
Time Perspective:	Prospective
Official Title:	Parkin Mutations and Their Functional Consequences
Study Start Date :	June 2002
Study Completion Date :	May 2006

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Parkinson disease

MedlinePlus related topics: Parkinson's Disease

U.S. FDA Resources

Groups and Cohorts

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Patients presenting with Parkinson's disease, with a family history or not,
Minors presenting clinical signs of the disease,
Controls (without signs of the disease, matched by sex and age with the patients, relatives for the familial cases)

Exclusion Criteria:

Persons refusing to sign the informed consent,
Lack of clinical information

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00136721

Locations

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France
Hôpital Pitié-Salpêtrière
Paris, France, 75013

Sponsors and Collaborators

Institut National de la Santé Et de la Recherche Médicale, France

National Institutes of Health (NIH)

Investigators

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Principal Investigator:	Alexis Brice, MD	Assistance Publique - Hôpitaux de Paris, University Paris 6

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications of Results:

Rawal N, Periquet M, Lohmann E, Lücking CB, Teive HA, Ambrosio G, Raskin S, Lincoln S, Hattori N, Guimaraes J, Horstink MW, Dos Santos Bele W, Brousolle E, Destée A, Mizuno Y, Farrer M, Deleuze JF, De Michele G, Agid Y, Dürr A, Brice A; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. New parkin mutations and atypical phenotypes in families with autosomal recessive parkinsonism. Neurology. 2003 Apr 22;60(8):1378-81.

Periquet M, Latouche M, Lohmann E, Rawal N, De Michele G, Ricard S, Teive H, Fraix V, Vidailhet M, Nicholl D, Barone P, Wood NW, Raskin S, Deleuze JF, Agid Y, Dürr A, Brice A; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. Parkin mutations are frequent in patients with isolated early-onset parkinsonism. Brain. 2003 Jun;126(Pt 6):1271-8.

Ibáñez P, Lohmann E, Pollak P, Durif F, Tranchant C, Agid Y, Dürr A, Brice A; French Parkinson's Disease Genetics Study Group. Absence of NR4A2 exon 1 mutations in 108 families with autosomal dominant Parkinson disease. Neurology. 2004 Jun 8;62(11):2133-4.

Ibáñez P, De Michele G, Bonifati V, Lohmann E, Thobois S, Pollak P, Agid Y, Heutink P, Dürr A, Brice A; French Parkinson's Disease Genetics Study Group. Screening for DJ-1 mutations in early onset autosomal recessive parkinsonism. Neurology. 2003 Nov 25;61(10):1429-31.

Lücking CB, Chesneau V, Lohmann E, Verpillat P, Dulac C, Bonnet AM, Gasparini F, Agid Y, Dürr A, Brice A. Coding polymorphisms in the parkin gene and susceptibility to Parkinson disease. Arch Neurol. 2003 Sep;60(9):1253-6.

Lohmann E, Periquet M, Bonifati V, Wood NW, De Michele G, Bonnet AM, Fraix V, Broussolle E, Horstink MW, Vidailhet M, Verpillat P, Gasser T, Nicholl D, Teive H, Raskin S, Rascol O, Destée A, Ruberg M, Gasparini F, Meco G, Agid Y, Durr A, Brice A; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. How much phenotypic variation can be attributed to parkin genotype? Ann Neurol. 2003 Aug;54(2):176-85.

Lesage S, Dürr A, Tazir M, Lohmann E, Leutenegger AL, Janin S, Pollak P, Brice A; French Parkinson's Disease Genetics Study Group. LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N Engl J Med. 2006 Jan 26;354(4):422-3.

Ibáñez P, Lesage S, Lohmann E, Thobois S, De Michele G, Borg M, Agid Y, Dürr A, Brice A; French Parkinson's Disease Genetics Study Group. Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa. Brain. 2006 Mar;129(Pt 3):686-94. Epub 2006 Jan 9.

Lesage S, Janin S, Lohmann E, Leutenegger AL, Leclere L, Viallet F, Pollak P, Durif F, Thobois S, Layet V, Vidailhet M, Agid Y, Dürr A, Brice A; French Parkinson's Disease Genetics Study Group, Bonnet AM, Borg M, Broussolle E, Damier P, Destée A, Martinez M, Penet C, Rasco O, Tison F, Tranchan C, Vérin M. LRRK2 exon 41 mutations in sporadic Parkinson disease in Europeans. Arch Neurol. 2007 Mar;64(3):425-30.

Leutenegger AL, Salih MA, Ibáñez P, Mukhtar MM, Lesage S, Arabi A, Lohmann E, Dürr A, Ahmed AE, Brice A. Juvenile-onset Parkinsonism as a result of the first mutation in the adenosine triphosphate orientation domain of PINK1. Arch Neurol. 2006 Sep;63(9):1257-61.

Lesage S, Magali P, Lohmann E, Lacomblez L, Teive H, Janin S, Cousin PY, Dürr A, Brice A; French Parkinson Disease Genetics Study Group. Deletion of the parkin and PACRG gene promoter in early-onset parkinsonism. Hum Mutat. 2007 Jan;28(1):27-32.

Brice A, Lohmann E, Ibanez P, Periquet M, Laine S, Debarges B, Lesage S, Dürr A. Phenotype/genotype correlations in Parkinson's disease. In: Relationships in Neurodegenerative Diseases, Cummings, Hardy, Poncet and Christen (Eds), Springer-Verlag Berlin Heidelberg Eds, 153-64, 2005.

Lohmann E, Dürr A, Ruberg M, Brice A. Parkin. In: Parkinson's Disease: Genetic and Pathogenesis, Dawson Eds, in press, 2006.

Brice A. [What can we learn from genes responsible for familial forms of Parkinson's disease?]. Bull Acad Natl Med. 2006 Feb;190(2):485-96; discussion 497-8. Review. French.

Ishihara L, Warren L, Gibson R, Amouri R, Lesage S, Dürr A, Tazir M, Wszolek ZK, Uitti RJ, Nichols WC, Griffith A, Hattori N, Leppert D, Watts R, Zabetian CP, Foroud TM, Farrer MJ, Brice A, Middleton L, Hentati F. Clinical features of Parkinson disease patients with homozygous leucine-rich repeat kinase 2 G2019S mutations. Arch Neurol. 2006 Sep;63(9):1250-4.

Foroud T, Pankratz N, Martinez M; PROGENI/GSPD-European Consortium. Chromosome 5 and Parkinson disease. Eur J Hum Genet. 2006 Oct;14(10):1106-10. Epub 2006 May 31.

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Responsible Party:	Alexis Brice, Inserm
ClinicalTrials.gov Identifier:	NCT00136721
Other Study ID Numbers:	9HD01H R01NS041723-01A1 ( U.S. NIH Grant/Contract )
First Posted:	August 29, 2005 Key Record Dates
Last Update Posted:	December 4, 2007
Last Verified:	December 2007

Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:


Parkinson's disease phenotype-genotype correlations mutations spectrum candidate genes

Additional relevant MeSH terms:

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Parkinson Disease Parkinsonian Disorders Basal Ganglia Diseases Brain Diseases	Central Nervous System Diseases Nervous System Diseases Movement Disorders Neurodegenerative Diseases

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