Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population

Autor: Karen Nuytemans, Bram Meeus, Dirk Goossens, Christine Van Broeckhoven, Sebastiaan Engelborghs, Jurgen Del-Favero, Peter Paul De Deyn, Marleen Van den Broeck, Philippe Pals, Nathalie Brouwers, Ellen Corsmit, Barbara A. Pickut, Jessie Theuns, Patrick Cras, David Crosiers
Přispěvatelé: Clinical sciences, Neurology
Rok vydání: 2009
Předmět:
Ubiquitin-Protein Ligases
Protein-Serine-Threonine Kinases/genetics
DNA Mutational Analysis
Protein Deglycase DJ-1
Population
Gene Dosage
Case-control studies
Protein Serine-Threonine Kinases
Protein Kinases/genetics
Biology
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
medicine.disease_cause
Belgium
Gene Frequency
Gene duplication
Genetics
medicine
Humans
alpha-Synuclein/genetics
Ubiquitin-Protein Ligases/genetics
Copy-number variation
Parkinson Disease/genetics
Mutation frequency
education
Belgium/epidemiology
Genetics (clinical)
Oncogene Proteins
Medicine(all)
education.field_of_study
Mutation
Intracellular Signaling Peptides and Proteins
PARK7
Parkinson Disease
Amplicon
LRRK2
Oncogene Proteins/genetics
Genetics
Population
alpha-Synuclein
Human medicine
mutation
Intracellular Signaling Peptides and Proteins/genetics
Protein Kinases
Zdroj: Human mutation
ISSN: 1098-1004
1059-7794
DOI: 10.1002/humu.21007
Popis: The relative contribution of simple mutations and copy number variations (CNVs) in SNCA, PARK2, PINK1, PARK7, and LRRK2 to the genetic etiology of Parkinson disease (PD) is still unclear because most studies did not completely analyze each gene. In a large group of Belgian PD patients (N=310) and control individuals (N=270), we determined the mutation frequency of both simple mutations and CNVs in these five PD genes, using direct sequencing, multiplex amplicon quantification (MAQ), and real-time PCR assays. Overall, we identified 14 novel heterozygous variants, of which 11 were absent in control individuals. We observed eight PARK2 (multiple) exon multiplications in PD patients and one exon deletion in a control individual. Furthermore, we identified one SNCA whole-gene duplication. The PARK2 and LRRK2 mutation frequencies in Belgian PD patients were similar to those reported in other studies. However, at this stage the true pathogenic nature of some heterozygous mutations in recessive genes remains elusive. Furthermore, though mutations is SNCA, PINK1, and PARK7 are rare, our identification of a SNCA duplication confirmed that screening of these genes remains meaningful. Hum Mutat 30:1–8, 2009. © 2009 Wiley-Liss, Inc.
Databáze: OpenAIRE
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