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Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease.
Mov Disord. 2009 Jan 30; 24(2):196-203.MD

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.

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Authors+Show Affiliations

Macedo MG
Section of Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. m.macedo@vumc.nl
Verbaan D
No affiliation info available
Fang Y
No affiliation info available
van Rooden SM
No affiliation info available
Visser M
No affiliation info available
Anar B
No affiliation info available
Uras A
No affiliation info available
Groen JL
No affiliation info available
Rizzu P
No affiliation info available
van Hilten JJ
No affiliation info available
Heutink P
No affiliation info available

MeSH

AdolescentAdultAge of OnsetAmino Acid SequenceConserved SequenceDNA Mutational AnalysisFemaleGenotypeHumansIntracellular Signaling Peptides and ProteinsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MaleMiddle AgedMolecular Sequence DataNetherlandsOncogene ProteinsParkinson DiseaseParkinsonian DisordersPhenotypeProtein Deglycase DJ-1Protein KinasesProtein-Serine-Threonine KinasesSequence AlignmentSequence Homology, Nucleic AcidUbiquitin-Protein LigasesYoung Adultalpha-Synuclein

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18973254

Citation

Macedo, Maria G., et al. "Genotypic and Phenotypic Characteristics of Dutch Patients With Early Onset Parkinson's Disease." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 24, no. 2, 2009, pp. 196-203.
Macedo MG, Verbaan D, Fang Y, et al. Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease. Mov Disord. 2009;24(2):196-203.
Macedo, M. G., Verbaan, D., Fang, Y., van Rooden, S. M., Visser, M., Anar, B., Uras, A., Groen, J. L., Rizzu, P., van Hilten, J. J., & Heutink, P. (2009). Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease. Movement Disorders : Official Journal of the Movement Disorder Society, 24(2), 196-203. https://doi.org/10.1002/mds.22287
Macedo MG, et al. Genotypic and Phenotypic Characteristics of Dutch Patients With Early Onset Parkinson's Disease. Mov Disord. 2009 Jan 30;24(2):196-203. PubMed PMID: 18973254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotypic and phenotypic characteristics of Dutch patients with early onset Parkinson's disease. AU - Macedo,Maria G, AU - Verbaan,Dagmar, AU - Fang,Yue, AU - van Rooden,Stephanie M, AU - Visser,Martine, AU - Anar,Burcu, AU - Uras,Antonella, AU - Groen,Justus L, AU - Rizzu,Patrizia, AU - van Hilten,Jacobus J, AU - Heutink,Peter, PY - 2008/11/1/pubmed PY - 2009/6/9/medline PY - 2008/11/1/entrez SP - 196 EP - 203 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 24 IS - 2 N2 - 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. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/18973254/Genotypic_and_phenotypic_characteristics_of_Dutch_patients_with_early_onset_Parkinson's_disease_ L2 - https://doi.org/10.1002/mds.22287 DB - PRIME DP - Unbound Medicine ER -