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How much phenotypic variation can be attributed to parkin genotype?

Lohmann, E; Periquet, M; Bonifati, V; Wood, NW; De Michele, G; Bonnet, AM; Fraix, V; ... European Consortium Genetic Suscep, ; + view all (2003) How much phenotypic variation can be attributed to parkin genotype? ANN NEUROL , 54 (2) 176 - 185. 10.1002/ana.10613.

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Abstract

To establish phenotype-genotype correlations in early-onset parkinsonism, we have compared the phenotype of a large series of 146 patients with and 250 patients without parkin mutations. Although no single sign distinguished the groups, patients with mutations had significantly earlier and more symmetrical onset, dystonia more often at onset and hyperreflexia, slower progression of the disease, and a tendency toward a greater response to levodopa despite lower doses. After forward stepwise multiple logistic regression analysis, dystonia at onset and brisk reflexes were not longer significantly different but were correlated with age at onset rather than the presence of the parkin mutation. Age at onset in carriers of parkin mutations varied as did the rate of progression of the disease: the younger the age at onset the slower the evolution. The genotype influenced the phenotype: carriers of at least one missense mutation had a higher United Parkinson's Disease Rating Scale motor score than those carrying two truncating mutations. The localization of the mutations was also important because missense mutations in functional domains of parkin resulted in earlier onset. Patients with a single heterozygous mutation had significantly later and more asymmetrical onset and more frequent levodopa-induced fluctuations and dystonia than patients with two mutations.

Type: Article
Title: How much phenotypic variation can be attributed to parkin genotype?
DOI: 10.1002/ana.10613
Keywords: RECESSIVE JUVENILE PARKINSONISM, EARLY-ONSET PARKINSONISM, UBIQUITIN-PROTEIN LIGASE, PSEUDO-DOMINANT INHERITANCE, GENE-MUTATIONS, HOMOZYGOUS DELETIONS, DIURNAL FLUCTUATION, JAPANESE FAMILIES, POINT MUTATIONS, ALPHA-SYNUCLEIN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: http://discovery.ucl.ac.uk/id/eprint/140163
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