Abstract
Recently, mutations in eukaryotic translation initiation factor 4G1 (EIF4G1) were reported as a rare cause of familial Parkinson’s disease (PD). We screened the 33 exons of EIF4G1 by high-resolution melting curve analysis for variants in our Central European cohort of 376 PD cases. Variant frequency was assessed in a total of 975 PD cases and 1,014 general population controls. Eight novel nonsynonymous and four synonymous variants were identified. In our cohort, novel and previously identified nonsynonymous variants were very rare. Although it is possible that our general population controls also comprise individuals who have or could develop PD in the future, the presence of the original mutation (EIF4G1 p.Arg1205 His) in three controls only, raises questions about the causality of this variant with regard to PD.
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Acknowledgments
We are very grateful to Jelena Golic, Susanne Lindhof, Katja Junghans, Regina Feldmann, and Sybille Frischholz for expert technical assistance.
Competing interests
The authors declare that they have no conflict of interest with regard to the above study. Full financial disclosures are listed below.
Dr. Schulte received a postdoctoral fellowship from Technische Universität München, Munich, Germany. Dr. Mollenhauer has received speaker honoraria from Orion Corporation and GlaxoSmithKline; serves as an Associate Editor for the Journal of Alzheimer Disease; holds or has pending patents re: Method of differentially diagnosing dementias; Novel ELISA-based quantification of alpha-synuclein proteins in cerebrospinal fluid and peripheral blood products using 384-well plates; and MicroRNA expression profiling of cerebrospinal fluid; serves as a consultant for Bayer Schering Pharma AG; and receives research support from Teva Pharmaceutical Industries Ltd., Desitin Pharmaceuticals, GmbH, Boehringer Ingelheim, GE Healthcare, the Michael J. Fox Foundation for Parkinson’s Research, the American Parkinson’s Disease Association, and the Stifterverband für die Deutsche Wissenschaft (Dr. Werner Jackstädt-Stipend). Dr. Zimprich reports no disclosures. Dr. Bereznai receives research support from the Hungarian National Innovation Office (TÁMOP-4-2-1/B-03/1/KMR-2010-001). Dr. Lichtner reports no disclosures. Dr. Haubenberger received an NINDS Intramural Competitive Fellowship and research report from the Austrian Science Fund (Erwin Schroedinger Fellowship, project# J2783-B09) and the NINDS Intramural Research Program. Dr. Pirker has received speaker honoraria and travel compensation from Boehringer Ingelheim, Novartis, Abbott Pharmaceuticals, Medtronic, and UCB. Dr. Brücke has received honoraria for lecturing and travel compensation from CSC, USB, Boehringer Ingelheim, Novartis, Aventis, GE Healthcare, Lundbeck, Merz, GlaxoSmithKline, and Pfizer. Dr. Molnar serves/has served on scientific advisory boards for Genzyme Europe B.V., received speaker honoria from Roche, serves as the Editor-in-Chief of the Hungarian edition of Neurology, and receives research support from the Hungarian National Innovation Office (TÁMOP-4-2-1/B-03/1/KMR-2010-001). Dr. Peters and Dr. Gieger report no disclosures. Dr. Trenkwalder serves on scientific advisory boards for Boehringer Ingelheim, Cephalon, Inc., UCB, Novartis, Mundipharma International Limited, and Solvay Pharmaceuticals, Inc.; has received speaker honoraria from Boehringer Ingelheim, Cephalon, Inc., UCB, Novartis, Pfizer Inc, and GlaxoSmithKline; serves on the editorial boards of Sleep Medicine and Movement Disorders and as an Associate Editor for Focus on Parkinson Disease. Dr. Winkelmann serves on a scientific advisory board for UCB; has received speaker honoraria from UCB and Boehringer Ingelheim; has filed a patent re: Winkelmann et al. Nat Genet 2007; and receives research support from the German RLS foundation, the Deutsche Forschungsgemeinschaft (DFG) and the Fritz Thyssen Foundation.
Funding
The study depicted herein was funded by institutional funding from Helmholtz Zentrum München, Munich, Germany. Recruitment of case and control cohorts was supported by institutional (Helmholtz Zentrum München, Munich, Germany) and government funding from the German Bundesministerium für Bildung und Forschung (03.2007-02.2011 FKZ 01ET0713), and the Hungarian National Innovation Office (TAMOP-4-2-1/B-03/1/KMR-2010-001).
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Schulte, E.C., Mollenhauer, B., Zimprich, A. et al. Variants in eukaryotic translation initiation factor 4G1 in sporadic Parkinson’s disease. Neurogenetics 13, 281–285 (2012). https://doi.org/10.1007/s10048-012-0334-9
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DOI: https://doi.org/10.1007/s10048-012-0334-9