Four Copies of SNCA Responsible for Autosomal Dominant Parkinson's Disease in Two Italian Siblings. (9th November 2015)

• Record Type: Journal Article
• Authors: Ferese, Rosangela; Modugno, Nicola; Campopiano, Rosa; Santilli, Marco; Zampatti, Stefania; Giardina, Emiliano; Nardone, Annamaria; Postorivo, Diana; Fornai, Francesco; Novelli, Giuseppe; Romoli, Edoardo; Ruggieri, Stefano; Gambardella, Stefano
• Other Names: Teive Hélio Academic Editor.
• Is Part Of: Parkinson's disease. Volume 2015(2015)
• Publication Date: 2015-11-09
• Subjects: Parkinson's disease -- Periodicals; Parkinson's disease -- Treatment -- Periodicals; 616.833005
• DOI: 10.1155/2015/546462
• Languages: English
• ISSNs: 2090-8083

Abstract

Abstract : Background . Parkinson's disease (PD) is mostly characterized by alpha-synuclein ( SNCA ) aggregation and loss of nigrostriatal dopamine-containing neurons. In this study a novel SNCA multiplication is described in two siblings affected by severe parkinsonism featuring early onset dyskinesia, psychiatric symptoms, and cognitive deterioration. Methods . SNCA dosage was performed using High-Density Comparative Genomic Hybridization Array (CGH-Array), Multiple Ligation Dependent Probe Amplification (MLPA), and Quantitative PCR (qPCR). Genetic analysis was associated with clinical evaluation. Results . Genetic analysis of siblings showed for the first time a 351 Kb triplication containing SNCA gene along with 6 exons of MMRN1 gene in 4q22.1 and a duplication of 1, 29 Mb of a genomic region flanking the triplication. Conclusions . The identification of this family indicates a novel mechanism of SNCA gene multiplication, which confirms the genomic instability in this region and provides data on the genotype-phenotype correlation in PD patients.