α-synuclein locus duplication as a cause of familial Parkinson's disease

• Published in: The Lancet (British edition) 2004-09, Vol.364 (9440), p.1167-1169
• Main Authors: Chartier-Harlin, Marie-Christine, Kachergus, Jennifer, Roumier, Christophe, Mouroux, Vincent, Douay, Xavier, Lincoln, Sarah, Levecque, Clotilde, Larvor, Lydie, Andrieux, Joris, Hulihan, Mary, Waucquier, Nawal, Defebvre, Luc, Amouyel, Philippe, Farrer, Matthew, Destée, Alain
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Aged; Aged, 80 and over; alpha-Synuclein; Female; Gene Dosage; Gene Duplication; Humans; In Situ Hybridization, Fluorescence; Lewy Body Disease - genetics; Male; Microsatellite Repeats; Middle Aged; Mutation, Missense; Nerve Tissue Proteins - genetics; Parkinson Disease - diagnosis; Parkinson Disease - genetics; Polymerase Chain Reaction; Synucleins
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(04)17103-1

Genomic triplication of the α-synuclein gene ( SNCA) has been reported to cause hereditary early-onset parkinsonism with dementia. These findings prompted us to screen for multiplication of the SNCA locus in nine families in whom parkinsonism segregates as an autosomal dominant trait. One kindred was identified with SNCA duplication by semiquantitative PCR and confirmed by fluorescent in-situ hybridisation analysis in peripheral leucocytes. By contrast with SNCA triplication families, the clinical phenotype of SNCA duplication closely resembles idiopathic Parkinson's disease, which has a late age-of-onset, progresses slowly, and in which neither cognitive decline nor dementia are prominent. These findings suggest a direct relation between SNCA gene dosage and disease progression.