6533b7cffe1ef96bd1259a1a
RESEARCH PRODUCT
A multi-centre clinico-genetic analysis of the VPS35 gene in Parkinson disease indicates reduced penetrance for disease-associated variants
Peter LichtnerRyan J. UittiGeorge D. MellickGeorgios M. HadjigeorgiouCarles Vilariño-güellKuo Chu YuehGeorg AuburgerPeter A. SilburnAndrew A. HicksSuzana GispertY. ZhaoGaëtan GarrauxTimothy LynchHarumi S. YomonoMaria BarcikowskaMiho MurataSuzanne LesageSuzanne LesageSuzanne LesageEng-king TanJoanne D. StocktonLars BertramOwen A. RossSung Sup ParkAlexander ZimprichBarbara Jasinska-mygaThomas GasserKarin WirdefeldtAlexis BriceAlexis BriceAlexis BriceRejko KrügerBeomseok JeonChristina M. LillVincent MokWataru SatakeHiroyuki TomiyamaTim M. StromMatthew J. FarrerCecile LibioulleGrzegorz OpalaPeter P. PramstallerIrene PichlerGrazia AnnesiDemetrius M. MaraganoreJessie TheunsJan O. AaslyMaria BoziAnna Krygowska-wajsJohn P. A. IoannidisZbigniew K. WszolekCarl E ClarkeKaren E. MorrisonKaren E. MorrisonNobutaka HattoriZygmunt JamrozikMaurizio F. FacherisManu SharmaThomas MeitngerTatsushi TodaAldo QuattroneChristine Van BroeckhovenEkaterina RogaevaLeonidas StefanisLeonidas StefanisGeorgia XiromerisiouDavid CrosiersJuei-jueng LinAnthony E. Langsubject
MaleParkinson's diseasePopulationVesicular Transport ProteinsLocus (genetics)DiseaseBiologyVPS35 protein humanBioinformaticsgenetics [Vesicular Transport Proteins]genetics [Parkinson Disease]Risk Factorsmedicinemetabolism [Vesicular Transport Proteins]GeneticsMissense mutationVPS35 GeneHumansGenetic epidemiologyGenetic Predisposition to Diseaseddc:6101506Genome-wideeducationGenetics (clinical)Genetic Association StudiesGeneticsVacuolar protein sortingeducation.field_of_studyGenotype-Phenotype CorrelationsParkinson DiseaseComplex traitsmedicine.diseasePenetranceddc:MutationFemaleHuman medicineParkinson-s diseasedescription
Abstract: Background Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease. Although additional missense variants were described, their pathogenic role yet remains inconclusive. Methods and results We performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort. Conclusions Our study apart from identifying the p. Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-11-01 | Journal of Medical Genetics |