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Parkin Gene (parkin + gene)

Distribution by Scientific Domains

Medical Sciences	87%

Selected Abstracts

Axonemal localization of Chlamydomonas PACRG, a homologue of the human Parkin -coregulated gene product

CYTOSKELETON, Issue 11 2007
Kazuho Ikeda
Abstract A homologue of mammalian PACRG was identified in Sarkosyl-extracted Chlamydomonas axonemes as a protein that may interact with Rib72 (a component of the protofilament ribbon within the outer doublet microtubules). PACRG is a protein whose expression is co-regulated with the Parkin gene implicated in Parkinson's disease. Although subsequent analyses did not confirm a Rib72-PACRG interaction, both proteins display similar localization in the axoneme. Immuno-localization of PACRG required pretreatment of the axoneme with Sarkosyl, suggesting that the antigen is buried in the wall of the microtubule. Indirect immunofluorescence localized PACRG to the entire length of the axoneme and the basal body, and immuno-electron microscopy showed that the PACRG antigen is densely distributed along the outer doublets in frayed axonemes. In thin-section images, the PACRG signals were frequently found between the A- and B-tubules of adjacent outer doublets. From these and other results, we propose that PACRG is a structural component of the doublet and triplet microtubules possibly involved in inter-tubule linkage. Cell Motil. Cytoskeleton, 2007. © 2007 Wiley-Liss, Inc. [source]

ATP13A2 variants in early-onset Parkinson's disease patients and controls,

MOVEMENT DISORDERS, Issue 14 2009
Ana Djarmati PhD
Abstract Four genes responsible for recessively inherited forms of Parkinson's disease (PD) have been identified, including the recently discovered ATP13A2 (PARK9) gene. Our objective was to investigate the role of this gene in a large cohort of PD patients and controls. We extensively screened all 29 exons of the ATP13A2 coding region in 112 patients with early-onset PD (EOPD; <40 years) of mostly European ethnic origin and of 55 controls. We identified four carriers (3.6%) of novel single heterozygous ATP13A2 missense changes that were absent in controls. Interestingly, the carrier of one of these variants also harbored two mutations in the Parkin gene. None of the carriers had atypical features previously described in patients with two mutated ATP13A2 alleles (Kufor,Rakeb syndrome). Our data suggest that two mutated ATP13A2 alleles are not a common cause of PD. Although heterozygous variants are present in a considerable number of patients, they are,based on this relatively small sample,not significantly more frequent in patients compared to controls. © 2009 Movement Disorder Society [source]

Chronic bilateral subthalamic deep brain stimulation in a patient with homozygous deletion in the Parkin gene

MOVEMENT DISORDERS, Issue 12 2004
Marianna Capecci MD
Abstract Chronic subthalamic nucleus deep brain stimulation (STN-DBS) is an efficacious treatment for idiopathic Parkinson's disease (PD) that cannot be further improved by medical therapy. We present a case of an individual with juvenile parkinsonism caused by homozygous deletion of exon 3 in the parkin gene with disabling long-term side-effects from levodopa who underwent bilateral STN neuromodulation. Parkin-linked parkinsonism may show clinical features different from sporadic PD, yet it shares levodopa responsiveness. Because levodopa responsiveness is a predictor of STN-DBS efficacy, we argued that this kind of surgical approach might be efficacious in hereditary parkin-linked juvenile parkinsonism. We evaluated clinical and functional assessment before and 12 months after surgery. The results showed that the Unified Parkinson Disease Rating Scales Motor score improved by 84% in our patient, the levodopa equivalent daily dose medication (LEDD) was reduced by 66%, and, finally, disabling and severe dyskinesias disappeared. © 2004 Movement Disorder Society [source]

Parkin gene variations in late-onset Parkinson's disease: comparison between Norwegian and German cohorts

ACTA NEUROLOGICA SCANDINAVICA, Issue 1 2006
A. M. Schlitter
Objectives ,, Mutations in the Parkin gene can cause autosomal recessive early-onset Parkinson's disease (PD). Recently, Parkin mutations were also suggested to play a role in the commoner late-onset forms of PD. Methods ,, We compared a German cohort of PD patients (95) with a Norwegian cohort of PD patients (96). Both cohorts have predominant late-onset form of PD. Mutation and polymorphism frequencies were compared via single-strand conformation polymorphism and sequence analyses. Results ,, Three heterozygous missense mutations (Arg256Cys, Arg402Cys and Thr240Met) were found in late-onset PD patients in the German patient cohort (1.6%). A missense mutation (Arg402Cys) was also found in one of 149 healthy control subjects (0.3%). Only one heterozygous missense mutation (Arg256Cys) was identified in a Norwegian patient suffering from late-onset PD (0.5%). The frequencies of four known single nucleotide polymorphisms significantly differ between the two distant European populations. Conclusion ,, The results support the hypothesis that heterozygous mutations in the Parkin gene may act as susceptibility alleles for late-onset forms of PD in rare cases. [source]

Low frequency of Parkin, Tyrosine Hydroxylase, and GTP Cyclohydrolase I gene mutations in a Danish population of early-onset Parkinson's Disease

EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2006
J. M. Hertz
Autosomal recessive Parkinson's disease (PD) with early-onset may be caused by mutations in the parkin gene (PARK2). We have ascertained 87 Danish patients with an early-onset form of PD (age at onset ,40 years, or ,50 years if family history is positive) in a multicenter study in order to determine the frequency of PARK2 mutations. Analysis of the GTP cyclohydrolase I gene (GCH1) and the tyrosine hydroxylase gene (TH), mutated in dopa-responsive dystonia and juvenile PD, have also been included. Ten different PARK2 mutations were identified in 10 patients. Two of the patients (2.3%) were found to have homozygous or compound heterozygous mutations, and eight of the patients (9.2%) were found to be heterozygous. A mutation has been identified in 10.4% of the sporadic cases and in 15.0% of cases with a positive family history of PD. One patient was found to be heterozygous for both a PARK2 mutation and a missense mutation (A6T) in TH of unknown significance. It cannot be excluded that both mutations contribute to the phenotype. No other putative disease causing TH or GCH1 mutations were found. In conclusion, homozygous, or compound heterozygous PARK2 mutations, and mutations in GCH1 and TH, are rare even in a population of PD patients with early-onset of the disease. [source]

Chronic bilateral subthalamic deep brain stimulation in a patient with homozygous deletion in the Parkin gene

Diagnostic considerations in juvenile parkinsonism

MOVEMENT DISORDERS, Issue 2 2004
Dominic C. Paviour MRCP
Abstract Juvenile parkinsonism (JP) describes patients in whom the clinical features of parkinsonism manifest before 21 years of age. Many reported cases that had a good response to levodopa have proved to have autosomal recessive juvenile parkinsonism (AR-JP) due to mutations in the parkin gene. With the exception of parkin mutations and dopa-responsive dystonia, most causes are associated with the presence of additional neurological signs, resulting from additional lesions outside of the basal ganglia. Lewy body pathology has only been reported in one case, suggesting that a juvenile form of idiopathic Parkinson's disease may be extremely rare. © 2003 Movement Disorder Society [source]

Involvement of spinal motor neurons in parkin-positive autosomal recessive juvenile parkinsonism

NEUROPATHOLOGY, Issue 1 2008
Shoichi Sasaki
We intensively examined the spinal cord of an autosomal recessive juvenile parkinsonism (ARJP) female patient with a homozygous exon 3 deletion in the parkin gene, anticipating a possible involvement of anterior horn neurons. Although the clinical features of the patient were consistent with parkinsonism as a result of parkin mutation, her tendon reflex was abolished in the lower limbs. This feature was in contrast with hyperreflexia, usually found in previous reports of ARJP. Histologically, on the level of the cervical, thoracic, and sacral spinal cord, anterior horn neurons were well preserved and normal. However, the lumbar spinal cord exhibited many swellings of proximal axons (spheroids) and degenerative changes in the somata of the large anterior horn neurons such as central chromatolysis, cystatin C-negative small eosinophilic inclusions, and eosinophilic Lewy body-like inclusions. Ultrastructurally, accumulations of neurofilaments and abnormal structures, such as inclusion bodies similar to skein-like inclusions and disorganized rough endoplasmic reticulum, were observed in the somata and neuronal processes. Lewy body-like inclusions in this study were positively immunostained for both ,-synuclein and ubiquitin that closely resemble Lewy bodies, but are different from Lewy body-like inclusions negatively immunostained for ,-synuclein in amyotrophic lateral sclerosis. These findings suggest that eosinophilic inclusions that closely resemble Lewy bodies may be formed in the spinal motor neurons of ARJP patients with parkin mutations and the motor neurons of these patients may be vulnerable to neurodegeneration. [source]