BACKGROUND: Major progress in genetic studies of Parkinson's disease (PD) and parkinsonism has been achieved in the last two decades. OBJECTIVE: We provide a brief review of the current status of PARK and non-PARK loci/genes, and discuss two new genes: eIF4G1 and VPS35. METHODS: The literature on PARK and non-PARK loci/genes was reviewed and some novel information on two new genes is provided. RESULTS: There are 18 PARK loci. The symptomatic carriers of these genes usually present with parkinsonism, although additional clinical features can be seen during the course of the disease. Carriers of non-PARK loci/genes frequently present with a mixed phenotype that includes parkinsonism and additional clinical features. Carriers of the eIF4G1 and VPS35 genes present with a parkinsonian phenotype. The pathology of eIF4G1 is of the α-synuclein type; the pathology of VPS35 is unknown. CONCLUSION: The current genetic classification of PD/parkinsonism genes is not ideal. The pathological classification based on the accumulation of particular proteins/inclusions is also misleading since there are kindred with a single mutation but pleomorphic pathology. A better classification of neurodegenerative conditions is needed. It is hoped that the genetic studies will lead to better therapies.
BACKGROUND: Major progress in genetic studies of Parkinson's disease (PD) and parkinsonism has been achieved in the last two decades. OBJECTIVE: We provide a brief review of the current status of PARK and non-PARK loci/genes, and discuss two new genes: eIF4G1 and VPS35. METHODS: The literature on PARK and non-PARK loci/genes was reviewed and some novel information on two new genes is provided. RESULTS: There are 18 PARK loci. The symptomatic carriers of these genes usually present with parkinsonism, although additional clinical features can be seen during the course of the disease. Carriers of non-PARK loci/genes frequently present with a mixed phenotype that includes parkinsonism and additional clinical features. Carriers of the eIF4G1 and VPS35 genes present with a parkinsonian phenotype. The pathology of eIF4G1 is of the α-synuclein type; the pathology of VPS35 is unknown. CONCLUSION: The current genetic classification of PD/parkinsonism genes is not ideal. The pathological classification based on the accumulation of particular proteins/inclusions is also misleading since there are kindred with a single mutation but pleomorphic pathology. A better classification of neurodegenerative conditions is needed. It is hoped that the genetic studies will lead to better therapies.
Authors: C Wider; L Skipper; A Solida; L Brown; M Farrer; D Dickson; Z K Wszolek; F J G Vingerhoets Journal: Parkinsonism Relat Disord Date: 2008-03-14 Impact factor: 4.891
Authors: Carles Vilariño-Güell; Christian Wider; Owen A Ross; Justus C Dachsel; Jennifer M Kachergus; Sarah J Lincoln; Alexandra I Soto-Ortolaza; Stephanie A Cobb; Greggory J Wilhoite; Justin A Bacon; Bahareh Behrouz; Heather L Melrose; Emna Hentati; Andreas Puschmann; Daniel M Evans; Elizabeth Conibear; Wyeth W Wasserman; Jan O Aasly; Pierre R Burkhard; Ruth Djaldetti; Joseph Ghika; Faycal Hentati; Anna Krygowska-Wajs; Tim Lynch; Eldad Melamed; Alex Rajput; Ali H Rajput; Alessandra Solida; Ruey-Meei Wu; Ryan J Uitti; Zbigniew K Wszolek; François Vingerhoets; Matthew J Farrer Journal: Am J Hum Genet Date: 2011-07-15 Impact factor: 11.025
Authors: Florian Giesert; Andreas Hofmann; Alexander Bürger; Julia Zerle; Karina Kloos; Ulrich Hafen; Luise Ernst; Jingzhong Zhang; Daniela Maria Vogt-Weisenhorn; Wolfgang Wurst Journal: PLoS One Date: 2013-05-10 Impact factor: 3.240
Authors: Marco A S Baptista; Kuldip D Dave; Niketa P Sheth; Shehan N De Silva; Kirsten M Carlson; Yasmin N Aziz; Brian K Fiske; Todd B Sherer; Mark A Frasier Journal: Dis Model Mech Date: 2013-09-12 Impact factor: 5.758