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

Karen Nuytemans, Bram Meeus, David Crosiers, Nathalie Brouwers, Dirk Goossens, Sebastiaan Engelborghs, Philippe Pals, Barbara Pickut, Marleen Van Den Broeck, Ellen Corsmit, Patrick Cras, Peter P. De Deyn, Jurgen Del-Favero, Christine Van Broeckhoven, Jessie Theuns

Research output: Contribution to journalArticle

51 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1054-1061
Number of pages8
JournalHuman mutation
Volume30
Issue number7
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

Keywords

  • CNV
  • LRRK2
  • PARK2
  • Parkinson disease
  • SNCA

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Nuytemans, K., Meeus, B., Crosiers, D., Brouwers, N., Goossens, D., Engelborghs, S., Pals, P., Pickut, B., Van Den Broeck, M., Corsmit, E., Cras, P., De Deyn, P. P., Del-Favero, J., Van Broeckhoven, C., & Theuns, J. (2009). Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population. Human mutation, 30(7), 1054-1061. https://doi.org/10.1002/humu.21007