title: Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population.
abstract: 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.
authors.affiliation: Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Nuytemans
authors.forename: Bram
authors.initials: B
authors.lastname: Meeus
authors.forename: David
authors.initials: D
authors.lastname: Crosiers
authors.forename: Nathalie
authors.initials: N
authors.lastname: Brouwers
authors.forename: Dirk
authors.initials: D
authors.lastname: Goossens
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.forename: Philippe
authors.initials: P
authors.lastname: Pals
authors.forename: Barbara
authors.initials: B
authors.lastname: Pickut
authors.forename: Marleen
authors.initials: M
authors.lastname: Van den Broeck
authors.forename: Ellen
authors.initials: E
authors.lastname: Corsmit
authors.forename: Patrick
authors.initials: P
authors.lastname: Cras
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn
authors.forename: Jurgen
authors.initials: J
authors.lastname: Del-Favero
authors.forename: Christine
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: Jessie
authors.initials: J
authors.lastname: Theuns
mesh_terms: D001530:Belgium / Q000453:epidemiology; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D018628:Gene Dosage; D005787:Gene Frequency; D005828:Genetics, Population; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D051844:alpha-Synuclein / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D051844:alpha-Synuclein; D000099202:PTEN-Induced Putative Kinase; C497604:SNCA protein, human; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human