Journal Article

Mutational analysis of the <i>PINK1</i> gene in early-onset parkinsonism in Europe and North Africa

Pablo Ibáñez, Suzanne Lesage, Ebba Lohmann, Stéphane Thobois, Giuseppe De Michele, Michel Borg, Yves Agid, Alexandra Dürr and Alexis Brice

in Brain

Published on behalf of The Guarantors of Brain

Volume 129, issue 3, pages 686-694
Published in print March 2006 | ISSN: 0006-8950
Published online January 2006 | e-ISSN: 1460-2156 | DOI:
Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa

Show Summary Details


Parkinson's disease is a frequent disorder caused primarily by the loss of dopaminergic neurons of the substantia nigra. Mutations in the PTEN-induced kinase (PINK1) gene, in addition to those in parkin and DJ-1, have been found in families with recessive early-onset Parkinson's disease. We screened for parkin and PINK1 mutations in a panel of 177 autosomal recessive Parkinson's disease families with ages at onset ≤60 years, mostly from Europe. In 7 unrelated families, we identified 10 pathogenic PINK1 mutations (5 missense, 2 nonsense and 3 frameshift deletion mutations), 8 of which were novel. All the mutations were in the homozygous or compound heterozygous states. Interestingly, pseudo-dominant inheritance was observed in a family with two different mutations. The clinical characteristics of 12 PINK1 patients and 114 parkin patients were similar, even for signs such as dystonia at onset and increased reflexes, which were thought to be specific to parkin. In contrast, onset in patients with PINK1 mutations was earlier and increased reflexes were found more frequently than in patients without PINK1 or parkin mutations. These results suggest that PINK1 is the second most frequent causative gene in early-onset Parkinson's disease with a slowly progressive phenotype, indistinguishable from early-onset patients with parkin mutations.

Keywords: early-onset parkinsonism; PINK1; parkin; mutation; EOP = early-onset parkinsonism; PINK1 = PTEN-induced putative kinase; UPDRS = Unified Parkinson's Disease Rating Scale

Journal Article.  6009 words.  Illustrated.

Subjects: Neurology ; Neuroscience

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.