Glucocerebrosidase mutations in a Serbian Parkinson's disease population

K. R. Kumar, A. Ramirez, A. Göbel, N. Kresojević, M. Svetel, K. Lohmann, C. M Sue, A. Rolfs, J. R. Mazzulli, R. N. Alcalay, D. Krainc, C. Klein*, V. Kostic, A. Grünewald

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background and purpose: 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. Conclusion: Glucocerebrosidase mutations represent a PD risk factor in the Serbian population.

Original languageEnglish (US)
Pages (from-to)402-405
Number of pages4
JournalEuropean Journal of Neurology
Volume20
Issue number2
DOIs
StatePublished - Feb 1 2013

Fingerprint

Glucosylceramidase
Parkinson Disease
Mutation
Population
Haplotypes
Alleles
Serbia
Exons

Keywords

  • GBA
  • Gaucher disease
  • Glucocerebrosidase
  • Parkinson's disease
  • Serbian

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Kumar, K. R., Ramirez, A., Göbel, A., Kresojević, N., Svetel, M., Lohmann, K., ... Grünewald, A. (2013). Glucocerebrosidase mutations in a Serbian Parkinson's disease population. European Journal of Neurology, 20(2), 402-405. https://doi.org/10.1111/j.1468-1331.2012.03817.x
Kumar, K. R. ; Ramirez, A. ; Göbel, A. ; Kresojević, N. ; Svetel, M. ; Lohmann, K. ; M Sue, C. ; Rolfs, A. ; Mazzulli, J. R. ; Alcalay, R. N. ; Krainc, D. ; Klein, C. ; Kostic, V. ; Grünewald, A. / Glucocerebrosidase mutations in a Serbian Parkinson's disease population. In: European Journal of Neurology. 2013 ; Vol. 20, No. 2. pp. 402-405.
@article{d5e53c4beb5448c79d8985397f03574f,
title = "Glucocerebrosidase mutations in a Serbian Parkinson's disease population",
abstract = "Background and purpose: 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. Conclusion: Glucocerebrosidase mutations represent a PD risk factor in the Serbian population.",
keywords = "GBA, Gaucher disease, Glucocerebrosidase, Parkinson's disease, Serbian",
author = "Kumar, {K. R.} and A. Ramirez and A. G{\"o}bel and N. Kresojević and M. Svetel and K. Lohmann and {M Sue}, C. and A. Rolfs and Mazzulli, {J. R.} and Alcalay, {R. N.} and D. Krainc and C. Klein and V. Kostic and A. Gr{\"u}newald",
year = "2013",
month = "2",
day = "1",
doi = "10.1111/j.1468-1331.2012.03817.x",
language = "English (US)",
volume = "20",
pages = "402--405",
journal = "European Journal of Neurology",
issn = "1351-5101",
publisher = "Wiley-Blackwell",
number = "2",

}

Kumar, KR, Ramirez, A, Göbel, A, Kresojević, N, Svetel, M, Lohmann, K, M Sue, C, Rolfs, A, Mazzulli, JR, Alcalay, RN, Krainc, D, Klein, C, Kostic, V & Grünewald, A 2013, 'Glucocerebrosidase mutations in a Serbian Parkinson's disease population', European Journal of Neurology, vol. 20, no. 2, pp. 402-405. https://doi.org/10.1111/j.1468-1331.2012.03817.x

Glucocerebrosidase mutations in a Serbian Parkinson's disease population. / Kumar, K. R.; Ramirez, A.; Göbel, A.; Kresojević, N.; Svetel, M.; Lohmann, K.; M Sue, C.; Rolfs, A.; Mazzulli, J. R.; Alcalay, R. N.; Krainc, D.; Klein, C.; Kostic, V.; Grünewald, A.

In: European Journal of Neurology, Vol. 20, No. 2, 01.02.2013, p. 402-405.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Glucocerebrosidase mutations in a Serbian Parkinson's disease population

AU - Kumar, K. R.

AU - Ramirez, A.

AU - Göbel, A.

AU - Kresojević, N.

AU - Svetel, M.

AU - Lohmann, K.

AU - M Sue, C.

AU - Rolfs, A.

AU - Mazzulli, J. R.

AU - Alcalay, R. N.

AU - Krainc, D.

AU - Klein, C.

AU - Kostic, V.

AU - Grünewald, A.

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Background and purpose: 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. Conclusion: Glucocerebrosidase mutations represent a PD risk factor in the Serbian population.

AB - Background and purpose: 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. Conclusion: Glucocerebrosidase mutations represent a PD risk factor in the Serbian population.

KW - GBA

KW - Gaucher disease

KW - Glucocerebrosidase

KW - Parkinson's disease

KW - Serbian

UR - http://www.scopus.com/inward/record.url?scp=84872386771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872386771&partnerID=8YFLogxK

U2 - 10.1111/j.1468-1331.2012.03817.x

DO - 10.1111/j.1468-1331.2012.03817.x

M3 - Article

VL - 20

SP - 402

EP - 405

JO - European Journal of Neurology

JF - European Journal of Neurology

SN - 1351-5101

IS - 2

ER -

Kumar KR, Ramirez A, Göbel A, Kresojević N, Svetel M, Lohmann K et al. Glucocerebrosidase mutations in a Serbian Parkinson's disease population. European Journal of Neurology. 2013 Feb 1;20(2):402-405. https://doi.org/10.1111/j.1468-1331.2012.03817.x