Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease.
Identifieur interne : 001F45 ( PubMed/Corpus ); précédent : 001F44; suivant : 001F46Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease.
Auteurs : Maria G. Macedo ; Dagmar Verbaan ; Yue Fang ; Stephanie M. Van Rooden ; Martine Visser ; Burcu Anar ; Antonella Uras ; Justus L. Groen ; Patrizia Rizzu ; Jacobus J. Van Hilten ; Peter HeutinkSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2009.
English descriptors
- KwdEn :
- Adolescent, Adult, Age of Onset, Amino Acid Sequence, Conserved Sequence, DNA Mutational Analysis, Female, Genotype, Humans, Intracellular Signaling Peptides and Proteins (genetics), Male, Middle Aged, Molecular Sequence Data, Netherlands (epidemiology), Oncogene Proteins (genetics), Parkinson Disease (epidemiology), Parkinson Disease (genetics), Parkinsonian Disorders (epidemiology), Parkinsonian Disorders (genetics), Phenotype, Protein Kinases (genetics), Protein-Serine-Threonine Kinases (genetics), Sequence Alignment, Sequence Homology, Nucleic Acid, Ubiquitin-Protein Ligases (genetics), Young Adult, alpha-Synuclein (genetics).
- MESH :
- chemical , genetics : Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Protein Kinases, Protein-Serine-Threonine Kinases, Ubiquitin-Protein Ligases, alpha-Synuclein.
- geographic , epidemiology : Netherlands.
- epidemiology : Parkinson Disease, Parkinsonian Disorders.
- genetics : Parkinson Disease, Parkinsonian Disorders.
- Adolescent, Adult, Age of Onset, Amino Acid Sequence, Conserved Sequence, DNA Mutational Analysis, Female, Genotype, Humans, Male, Middle Aged, Molecular Sequence Data, Phenotype, Sequence Alignment, Sequence Homology, Nucleic Acid, Young Adult.
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 < or = 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.
DOI: 10.1002/mds.22287
PubMed: 18973254
Links to Exploration step
pubmed:18973254Le document en format XML
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<author><name sortKey="Verbaan, Dagmar" sort="Verbaan, Dagmar" uniqKey="Verbaan D" first="Dagmar" last="Verbaan">Dagmar Verbaan</name>
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<term>Amino Acid Sequence</term>
<term>Conserved Sequence</term>
<term>DNA Mutational Analysis</term>
<term>Female</term>
<term>Genotype</term>
<term>Humans</term>
<term>Intracellular Signaling Peptides and Proteins (genetics)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Molecular Sequence Data</term>
<term>Netherlands (epidemiology)</term>
<term>Oncogene Proteins (genetics)</term>
<term>Parkinson Disease (epidemiology)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinsonian Disorders (epidemiology)</term>
<term>Parkinsonian Disorders (genetics)</term>
<term>Phenotype</term>
<term>Protein Kinases (genetics)</term>
<term>Protein-Serine-Threonine Kinases (genetics)</term>
<term>Sequence Alignment</term>
<term>Sequence Homology, Nucleic Acid</term>
<term>Ubiquitin-Protein Ligases (genetics)</term>
<term>Young Adult</term>
<term>alpha-Synuclein (genetics)</term>
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<term>Oncogene Proteins</term>
<term>Protein Kinases</term>
<term>Protein-Serine-Threonine Kinases</term>
<term>Ubiquitin-Protein Ligases</term>
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<term>DNA Mutational Analysis</term>
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<term>Genotype</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Molecular Sequence Data</term>
<term>Phenotype</term>
<term>Sequence Alignment</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 < or = 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>
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<Abstract><AbstractText>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 < or = 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.</AbstractText>
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