Genotypic and Phenotypic Characteristics of Dutch Patients with Early Onset Parkinson's Disease
Identifieur interne : 002F58 ( Main/Merge ); précédent : 002F57; suivant : 002F59Genotypic and Phenotypic Characteristics of Dutch Patients with Early Onset Parkinson's Disease
Auteurs : Maria G. Macedo [Pays-Bas] ; Dagmar Verbaan [Pays-Bas] ; YUE FANG [Pays-Bas] ; Stephanie M. Van Rooden [Pays-Bas] ; Martine Visser [Pays-Bas] ; Burcu Anar [Pays-Bas] ; Antonella Uras [Pays-Bas] ; Justus L. Groen [Pays-Bas] ; Patrizia Rizzu [Pays-Bas] ; Jacobus J. Van Hilten [Pays-Bas] ; Peter Heutink [Pays-Bas]Source :
- Movement disorders [ 0885-3185 ] ; 2009.
Descripteurs français
- Pascal (Inist)
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- topic : Homme.
English descriptors
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Abstract
Early onset Parkinson's disease (EOPD) has been associated with mutations in the Parkin, DJ-1. PINK1. LRRK2, and SNCA genes. The aim of this study is to assess the contribution of these genes in a Dutch EOPD cohort and the phenotypic characteristics of the mutation carriers. A total of 187 unrelated Dutch EOPD patients (age at onset < 50 years) were phenotyped and screened for mutations in all exons of Parkin, DJ-1, and PINK1 by direct sequencing and gene dosage analysis. Additionally, analysis of the A30P mutation and exon dosage of SNCA and sequencing of exons 19,31,35,38,41, and 48 of LRRK2 was performed. Pathogenic variations could explain disease in 4% (7 of 187) of the patients including five patients carrying homozygous or compound heterozygous mutations in Parkin, one with a novel homozygous deletion in DJ-1 (P158Del) and one with a heterozygous mutation in LRRK2 (T2356I). We found seven novel mutations. The phenotypic characteristics of mutation carriers varied widely, comparable to the variability seen in sporadic EOPD. Parkin is the most frequently mutated gene in this EOPD cohort, followed by DJ-1, PINK1 and LRRK2. The low overall mutation frequency indicates that the extrapolation of mutation frequencies from other populations should be applied with caution.
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Genotypic and Phenotypic Characteristics of Dutch Patients with Early Onset Parkinson's Disease</title>
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<series><title level="j" type="main">Movement disorders</title>
<title level="j" type="abbreviated">Mov. disord.</title>
<idno type="ISSN">0885-3185</idno>
<imprint><date when="2009">2009</date>
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<seriesStmt><title level="j" type="main">Movement disorders</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dutch</term>
<term>Genotype</term>
<term>Human</term>
<term>Mutation</term>
<term>Nervous system diseases</term>
<term>Parkinson disease</term>
<term>Phenotype</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term>
<term>Pathologie du système nerveux</term>
<term>Génotype</term>
<term>Néerlandais</term>
<term>Homme</term>
<term>Mutation</term>
<term>Phénotype</term>
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<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
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<front><div type="abstract" xml:lang="en">Early onset Parkinson's disease (EOPD) has been associated with mutations in the Parkin, DJ-1. PINK1. LRRK2, and SNCA genes. The aim of this study is to assess the contribution of these genes in a Dutch EOPD cohort and the phenotypic characteristics of the mutation carriers. A total of 187 unrelated Dutch EOPD patients (age at onset < 50 years) were phenotyped and screened for mutations in all exons of Parkin, DJ-1, and PINK1 by direct sequencing and gene dosage analysis. Additionally, analysis of the A30P mutation and exon dosage of SNCA and sequencing of exons 19,31,35,38,41, and 48 of LRRK2 was performed. Pathogenic variations could explain disease in 4% (7 of 187) of the patients including five patients carrying homozygous or compound heterozygous mutations in Parkin, one with a novel homozygous deletion in DJ-1 (P158Del) and one with a heterozygous mutation in LRRK2 (T2356I). We found seven novel mutations. The phenotypic characteristics of mutation carriers varied widely, comparable to the variability seen in sporadic EOPD. Parkin is the most frequently mutated gene in this EOPD cohort, followed by DJ-1, PINK1 and LRRK2. The low overall mutation frequency indicates that the extrapolation of mutation frequencies from other populations should be applied with caution.</div>
</front>
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<tree><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Macedo, Maria G" sort="Macedo, Maria G" uniqKey="Macedo M" first="Maria G." last="Macedo">Maria G. Macedo</name>
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<name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name>
<name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name>
<name sortKey="Uras, Antonella" sort="Uras, Antonella" uniqKey="Uras A" first="Antonella" last="Uras">Antonella Uras</name>
<name sortKey="Van Hilten, Jacobus J" sort="Van Hilten, Jacobus J" uniqKey="Van Hilten J" first="Jacobus J." last="Van Hilten">Jacobus J. Van Hilten</name>
<name sortKey="Van Rooden, Stephanie M" sort="Van Rooden, Stephanie M" uniqKey="Van Rooden S" first="Stephanie M." last="Van Rooden">Stephanie M. Van Rooden</name>
<name sortKey="Verbaan, Dagmar" sort="Verbaan, Dagmar" uniqKey="Verbaan D" first="Dagmar" last="Verbaan">Dagmar Verbaan</name>
<name sortKey="Visser, Martine" sort="Visser, Martine" uniqKey="Visser M" first="Martine" last="Visser">Martine Visser</name>
<name sortKey="Yue Fang" sort="Yue Fang" uniqKey="Yue Fang" last="Yue Fang">YUE FANG</name>
</country>
</tree>
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