Premium
Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population
Author(s) -
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.,
DelFavero Jurgen,
Van Broeckhoven Christine,
Theuns Jessie
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21007
Subject(s) - lrrk2 , biology , genetics , gene duplication , copy number variation , multiplex ligation dependent probe amplification , amplicon , exon , gene , mutation , mutation frequency , multiplex , population , polymerase chain reaction , genome , medicine , environmental health
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.