1. Glucocerebrosidase mutations in a Serbian Parkinson’s disease population

Glucocerebrosidase mutations in a Serbian Parkinson’s disease population

Kishore Kumar, MD 1, 2 Alfredo Ramirez, MD 1, 3 Anna Göbel, MD 1 Nikola Kresojevic, MD 4 Prof. Marina Svetel, MD 4 Katja Lohmann, PhD 1 Prof. Carolyn Sue, PhD 2 Prof. Arndt Rolfs, MD 5 Joseph R. Mazzulli, PhD 6 Roy N. Alcalay, MD 7 Dimitri Krainc, MD 6 Prof. Christine Klein, MD 1 Vladimir Kostić, MD 4 Anne Grünewald, PhD 1
1 University of Luebeck 2 University of Sidney 3 University Hospital Bonn 4 University of Belgrad 5 University of Rostock 6 Harvard Medical School Boston 7 Columbia University
June 12, 2012

European Journal of Neurology 2013, 20: 402–405
doi:10.1111/j.1468-1331.2012.03817.x

Gaucher disease (GD) is caused by homozygous or compound heterozygous mutations in the b-glucocerebrosidase (GBA) gene. GBA mutations can be classified according to phenotypic effects as mild (associated with ‘non-neuronopathic’ Type 1 GD) and severe or null (neuronopathic Type 2 or 3 disease) [1]. In addition to causing GD, GBA mutations are also susceptibility factors for Parkinson’s disease (PD) [2,3]. Most studies show an association between GBA mutations and PD, although this association was not found in a Norwegian population [4]. The frequency of the different GBA mutations varies according to ethnicity. In Ashkenazi Jewish (AJ) and French populations, N370S is the most frequent mutation [2,3], whereas in Asian populations, the L444P mutation is more common [3]. PD patients with GBA mutations present earlier and are more likely to have a positive family history and cognitive changes [3]. A common founder has been observed for the N370S mutation in AJs and in several European populations [5 – 7]. In the present study, we elucidated, for the first time, the role of GBA mutations in PD in the Serbian population, including mutational analysis of exons 8–11, genotype–phenotype comparisons, and haplotyping for the N370S mutation.