Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa
Identifieur interne : 001255 ( Main/Curation ); précédent : 001254; suivant : 001256Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa
Auteurs : Pablo Iba N Ez ; Suzanne Lesage ; Ebba Lohmann ; Ste Phane Thobois ; Giuseppe De Michele [Italie] ; Michel Borg ; Yves Agid ; Alexandra Du Rr ; Alexis BriceSource :
- Brain [ 0006-8950 ] ; 2006-03.
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- KwdEn :
Abstract
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.
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DOI: 10.1093/brain/awl005
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<series><title level="j">Brain</title>
<title level="j" type="abbrev">Brain</title>
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<idno type="eISSN">1460-2156</idno>
<imprint><publisher>Oxford University Press</publisher>
<date type="published" when="2006-03">2006-03</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>EOP = early-onset parkinsonism</term>
<term>PINK1</term>
<term>PINK1 = PTEN-induced putative kinase</term>
<term>UPDRS = Unified Parkinson's Disease Rating Scale</term>
<term>early-onset parkinsonism</term>
<term>mutation</term>
<term>parkin</term>
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<front><div type="abstract" xml:lang="en">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.</div>
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