GCH1 in early-onset Parkinson's disease

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dc.contributor.authorCobb, S. A.
dc.contributor.authorWider, C.
dc.contributor.authorRoss, O. A.
dc.contributor.authorMata, I. F.
dc.contributor.authorAdler, C. H.
dc.contributor.authorRajput, A.
dc.contributor.authorRajput, A. H.
dc.contributor.authorWu, R. M.
dc.contributor.authorHauser, R.
dc.contributor.authorJosephs, K. A.
dc.contributor.authorCarr, J.
dc.contributor.authorGwinn, K.
dc.contributor.authorHeckman, M. G.
dc.contributor.authorAasly, J. O.
dc.contributor.authorLynch, T.
dc.contributor.authorUitti, R. J.
dc.contributor.authorWszolek, Z. K.
dc.contributor.authorKapatos, G.
dc.contributor.authorFarrer, M. J.
dc.date.accessioned2011-05-15T16:17:25Z
dc.date.available2011-05-15T16:17:25Z
dc.date.issued2009
dc.description.abstractMutations in GTP-cyclohydrolase 1 (GCH1) cause autosomal dominant dopa-responsive dystonia (DRD), characterized by childhood-onset foot dystonia that later generalizes. DRD patients frequently present with associated Parkinsonism. Conversely, early-onset Parkinson's disease (EOPD) patients commonly display dystonia. Herein, we investigated the frequency of GCH1 mutations in a series of 53 familial EOPD patients (21 with dystonia) and screened them for mutations in PRKN, PINK1, and DJ-1. In addition, we examined a matched EOPD patient-control series for association of common variability at the GCH1 locus and EOPD susceptibility. No GCH1 coding change or copy-number abnormality was identified in familial EOPD patients. A novel 18-bp deletion was found in the proximal promoter (two patients, one control), which is expected to knock out two regulatory elements previously shown to regulate GCH1 transcription. No association was found between GCH1 variability and risk of EOPD. Fourteen (26.4%) familial EOPD patients had homozygous or compound heterozygous PRKN mutations. PRKN-positive patients were 10 years younger than PRKNnegative patients and had a twofold higher prevalence of dystonia. This study does not support a significant role for genetic variation at the GCH1 locus in EOPD. However, our results further highlight the relevance of PRKN screening in familial EOPD. © 2009 Movement Disorder Society.
dc.description.versionArticle
dc.identifier.citationMovement Disorders
dc.identifier.citation24
dc.identifier.citation14
dc.identifier.issn08853185
dc.identifier.other10.1002/mds.22729
dc.identifier.urihttp://hdl.handle.net/10019.1/14206
dc.subjectcytosine
dc.subjectDJ 1 protein
dc.subjectgene product
dc.subjectguanine
dc.subjectguanosine triphosphate cyclohydrolase I
dc.subjectparkin
dc.subjectprotein pink1
dc.subjectunclassified drug
dc.subjectadolescent
dc.subjectadult
dc.subjectarticle
dc.subjectcontrolled study
dc.subjectdystonia
dc.subjectfemale
dc.subjectgene deletion
dc.subjectgene duplication
dc.subjectgene frequency
dc.subjectgene locus
dc.subjectgene sequence
dc.subjectgenetic variability
dc.subjectheterozygote
dc.subjecthomozygote
dc.subjecthuman
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectmutation rate
dc.subjectonset age
dc.subjectParkinson disease
dc.subjectpriority journal
dc.subjectsingle nucleotide polymorphism
dc.subjectAdult
dc.subjectAge of Onset
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectDNA
dc.subjectDNA Mutational Analysis
dc.subjectEuropean Continental Ancestry Group
dc.subjectFemale
dc.subjectGene Dosage
dc.subjectGene Frequency
dc.subjectGenetic Variation
dc.subjectGTP Cyclohydrolase
dc.subjectHumans
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectMale
dc.subjectMiddle Aged
dc.subjectNorth America
dc.subjectOncogene Proteins
dc.subjectParkinson Disease
dc.subjectPolymorphism, Single Nucleotide
dc.subjectProtein Kinases
dc.subjectUbiquitin-Protein Ligases
dc.titleGCH1 in early-onset Parkinson's disease
dc.typeArticle
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