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 language | English (US) |
|---|---|
| Pages (from-to) | 1054-1061 |
| Number of pages | 8 |
| Journal | Human Mutation |
| Volume | 30 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2009 |
| Externally published | Yes |
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Keywords
- CNV
- LRRK2
- PARK2
- Parkinson disease
- SNCA
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)
Cite this
Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population. / Nuytemans, Karen; Meeus, Bram; Crosiers, David; Brouwers, Nathalie; Goossens, Dirk; Engelborghs, Sebastiaan; Pals, Philippe; Pickut, Barbara; Van Den Broeck, Marleen; Corsmit, Ellen; Cras, Patrick; De Deyn, Peter P.; Del-Favero, Jurgen; Van Broeckhoven, Christine; Theuns, Jessie.
In: Human Mutation, Vol. 30, No. 7, 01.07.2009, p. 1054-1061.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population
AU - Nuytemans, Karen
AU - Meeus, Bram
AU - Crosiers, David
AU - Brouwers, Nathalie
AU - Goossens, Dirk
AU - Engelborghs, Sebastiaan
AU - Pals, Philippe
AU - Pickut, Barbara
AU - Van Den Broeck, Marleen
AU - Corsmit, Ellen
AU - Cras, Patrick
AU - De Deyn, Peter P.
AU - Del-Favero, Jurgen
AU - Van Broeckhoven, Christine
AU - Theuns, Jessie
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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.
AB - 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.
KW - CNV
KW - LRRK2
KW - PARK2
KW - Parkinson disease
KW - SNCA
UR - http://www.scopus.com/inward/record.url?scp=67649637695&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67649637695&partnerID=8YFLogxK
U2 - 10.1002/humu.21007
DO - 10.1002/humu.21007
M3 - Article
C2 - 19405094
AN - SCOPUS:67649637695
VL - 30
SP - 1054
EP - 1061
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 7
ER -