Glucocerebrosidase mutations in a Serbian Parkinson's disease population.
OBJECTIVE
To screen for glucocerebrosidase (GBA) mutations in a Serbian Parkinson's disease (PD) population.


METHODS
Glucocerebrosidase exons 8-11 harbouring the most common mutations were sequenced in 360 patients with PD and 348 controls from Serbia. Haplotype analysis was performed for the N370S mutation and compared with German and Ashkenazi Jewish carriers.


RESULTS
Glucocerebrosidase mutations were significantly more frequent in patients with PD (21/360; 5.8%) vs. controls (5/348; 1.4%; OR = 4.25; CI, 1.58-11.40; P = 0.0041). Two patients with PD carried homozygous or compound heterozygous mutations in GBA. The N370S mutation accounted for about half of the mutated alleles in patients (10/23) but was absent amongst controls. Three novel variants were detected including two non-synonymous variants (D380V, N392S) in the patient group and one synonymous change (V459V) in a control. Carriers of the D409H mutation were also sequenced for H255Q, and all were found to carry the [D409H; H255Q] double-mutant allele. Genotyping suggested a common haplotype for all N370S carriers.


CONCLUSIONS
Glucocerebrosidase mutations represent a PD risk factor in the Serbian population.
Department of Neurology, Section of Clinical and Molecular Neurogenetics, University of Lübeck, Lübeck, Germany.
K R
KR
Kumar
A
A
Ramirez
A
A
Göbel
N
N
Kresojević
M
M
Svetel
K
K
Lohmann
C
C
M Sue
A
A
Rolfs
J R
JR
Mazzulli
R N
RN
Alcalay
D
D
Krainc
C
C
Klein
V
V
Kostic
A
A
Grünewald
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D055771:Serbia; D044465:White People / Q000235:genetics*
D005962:Glucosylceramidase