Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease
Identifieur interne : 002288 ( Main/Exploration ); précédent : 002287; suivant : 002289Genotypic 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 ] ; 2009-01-30.
Descripteurs français
- Pascal (Inist)
- Wicri :
English descriptors
- KwdEn :
- Adolescent, Adult, Age of Onset, Amino Acid Sequence, Conserved Sequence, DNA Mutational Analysis, Dutch, Female, Genotype, Human, Humans, Intracellular Signaling Peptides and Proteins (genetics), Male, Middle Aged, Molecular Sequence Data, Mutation, Nervous system diseases, Netherlands (epidemiology), Oncogene Proteins (genetics), Parkinson Disease (epidemiology), Parkinson Disease (genetics), Parkinson disease, Parkinson's disease, 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), genotype, mutations, phenotype.
- 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 ≤ 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. © 2008 Movement Disorder Society
Url:
DOI: 10.1002/mds.22287
Affiliations:
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Macedo</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Verbaan, Dagmar" sort="Verbaan, Dagmar" uniqKey="Verbaan D" first="Dagmar" last="Verbaan">Dagmar Verbaan</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Neurology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Fang, Yue" sort="Fang, Yue" uniqKey="Fang Y" first="Yue" last="Fang">Yue Fang</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><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><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Neurology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Visser, Martine" sort="Visser, Martine" uniqKey="Visser M" first="Martine" last="Visser">Martine Visser</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Neurology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Anar, Burcu" sort="Anar, Burcu" uniqKey="Anar B" first="Burcu" last="Anar">Burcu Anar</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Uras, Antonella" sort="Uras, Antonella" uniqKey="Uras A" first="Antonella" last="Uras">Antonella Uras</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Groen, Justus L" sort="Groen, Justus L" uniqKey="Groen J" first="Justus L." last="Groen">Justus L. Groen</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Rizzu, Patrizia" sort="Rizzu, Patrizia" uniqKey="Rizzu P" first="Patrizia" last="Rizzu">Patrizia Rizzu</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><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><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Neurology, Leiden University Medical Center, Leiden</wicri:regionArea><placeName><settlement type="city">Leyde</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Heutink, Peter" sort="Heutink, Peter" uniqKey="Heutink P" first="Peter" last="Heutink">Peter Heutink</name><affiliation wicri:level="3"><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="sub">Official Journal of the Movement Disorder Society</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-01-30">2009-01-30</date><biblScope unit="vol">24</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="196">196</biblScope><biblScope unit="page" to="203">203</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">DE638C36AA94E663C451706BAB4E28460A4CBCB9</idno><idno type="DOI">10.1002/mds.22287</idno><idno type="ArticleID">MDS22287</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Age of Onset</term><term>Amino Acid Sequence</term><term>Conserved Sequence</term><term>DNA Mutational Analysis</term><term>Dutch</term><term>Female</term><term>Genotype</term><term>Human</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>Mutation</term><term>Nervous system diseases</term><term>Netherlands (epidemiology)</term><term>Oncogene Proteins (genetics)</term><term>Parkinson Disease (epidemiology)</term><term>Parkinson Disease (genetics)</term><term>Parkinson disease</term><term>Parkinson's disease</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><term>genotype</term><term>mutations</term><term>phenotype</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term><term>Protein Kinases</term><term>Protein-Serine-Threonine Kinases</term><term>Ubiquitin-Protein Ligases</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="geographic" qualifier="epidemiology" xml:lang="en"><term>Netherlands</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>Parkinson Disease</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Adult</term><term>Age of Onset</term><term>Amino Acid Sequence</term><term>Conserved Sequence</term><term>DNA Mutational Analysis</term><term>Female</term><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><term>Sequence Homology, Nucleic Acid</term><term>Young Adult</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Génotype</term><term>Homme</term><term>Maladie de Parkinson</term><term>Mutation</term><term>Néerlandais</term><term>Pathologie du système nerveux</term><term>Phénotype</term></keywords><keywords scheme="Wicri" type="geographic" xml:lang="fr"><term>Pays-Bas</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><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. © 2008 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>Pays-Bas</li></country><region><li>Hollande-Méridionale</li><li>Hollande-Septentrionale</li></region><settlement><li>Amsterdam</li><li>Leyde</li></settlement></list><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></region><name sortKey="Anar, Burcu" sort="Anar, Burcu" uniqKey="Anar B" first="Burcu" last="Anar">Burcu Anar</name><name sortKey="Fang, Yue" sort="Fang, Yue" uniqKey="Fang Y" first="Yue" last="Fang">Yue Fang</name><name sortKey="Groen, Justus L" sort="Groen, Justus L" uniqKey="Groen J" first="Justus L." last="Groen">Justus L. Groen</name><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></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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