Italian PD Genetics Study Group French PD Genetics Study Group; European Consortium on Genetic Susceptibility in PD The parkin gene and its phenotype.Italian PD Genetics Study Group French PD Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
ABSTRACT Mutations of the parkin gene on chromosome 6 cause autosomal recessive, early onset parkinsonism. This is the most frequent form of monogenic parkinsonism so far identified. The associated phenotypical spectrum encompasses early onset, levodopa-responsive parkinsonism (average onset in the early 30s in Europe), and it overlaps with dopa-responsive dystonia in cases with the earliest onset, and with clinically typical Parkinson's disease in cases with later onset. Despite clinical features, Lewy bodies are not found at autopsy in brains of patients with parkin mutations. The parkin protein possesses ubiquitin ligase activity, which is abolished by the pathogenic mutations.
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- "Ubiquitin ELISA, cerebrospinal fluid, serum [42 – 45] Parkinson's disease Ubiquitin (+) Immunocytochemistry, brain specimen [57 – 59,62] Parkin (+) Immunocytochemistry, brain specimen  Parkin (+) PCR, peripheral blood leukocytes    Dementia with Lewy bodies Ubiquitin (+) Immunocytochemistry, brain specimen     Pick's disease Ubiquitin (+) Immunocytochemistry, brain specimen     Amyotrophic lateral sclerosis Ubiquitin (+) Immunocytochemistry, brain specimen   Huntington's disease Ubiquitin (+) Immunocytochemistry, brain specimen   Creutzfeld – Jakob disease Ubiquitin (z) RIA, cerebrospinal fluid  Cancer Renal cancer Proteasome subunits C2 and C9 (z) PCR, immunocytochemistry, tumor biopsy   20S Proteasome (z) ELISA, serum    Gastric cancer 20S Proteasome (z) ELISA, serum    Myeloid leukemia 20S Proteasome (z) ELISA, serum    Lymphoma 20S Proteasome (z) ELISA, serum   Thyroid carcinoma PA28-g (z) Western blot, immunocytochemistry, tumor biopsy  Breast, gastric, lung, brain, ovary, prostate, bladder, esophageal cancer p27 (#) Western blot, immunocytochemistry, tumor biopsy [86 – 91] Autoimmune diseases "
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ABSTRACT: Dystonia is a syndrome characterised by sustained muscle contractions, producing twisting, repetitive, and patterned movements, or abnormal postures. The dystonic syndromes include a large group of diseases that have been classified into various aetiological categories, such as primary, dystonia-plus, heredodegenerative, and secondary. The diverse clinical features of these disorders are reflected in the traditional clinical classification based on age at onset, distribution of symptoms, and site of onset. However, with an increased awareness of the molecular and environmental causes, the classification schemes have changed to reflect different genetic forms of dystonia. To date, at least 13 dystonic syndromes have been distinguished on a genetic basis and their loci are referred to as DYT1 to DYT13. This review focuses on the molecular and phenotypic features of the hereditary dystonias, with emphasis on recent advances.The Lancet Neurology 10/2002; 1(5):316-25. DOI:10.1016/S1474-4422(02)00137-0 · 21.82 Impact Factor
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ABSTRACT: Parkinson's disease was thought, until recently, to have little or no genetic component. This notion has changed with the identification of three genes, and the mapping of five others, that are linked to rare familial forms of the disease (FPD). The products of the identified genes, alpha-synuclein (PARK 1), parkin (PARK 2), and ubiquitin-C-hydrolase-L1 (PARK 5) are the subject of intense cell-biological and biochemical studies designed to elucidate the underlying mechanism of FPD pathogenesis. In addition, the complex genetics of idiopathic PD is beginning to be unraveled. Genetic information may prove to be useful in identifying new therapeutic targets and identifying the preclinical phase of PD, allowing treatment to begin sooner.Current Opinion in Cell Biology 11/2002; 14(5):653-60. DOI:10.1016/S0955-0674(02)00377-0 · 8.74 Impact Factor