title: Four Copies of SNCA Responsible for Autosomal Dominant Parkinson's Disease in Two Italian Siblings.
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.
authors.affiliation: IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy.
authors.forename: Rosangela
authors.initials: R
authors.lastname: Ferese
authors.affiliation: IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Modugno
authors.affiliation: IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Campopiano
authors.affiliation: IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Santilli
authors.affiliation: IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy ; Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, 00142 Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Zampatti
authors.affiliation: Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, 00142 Rome, Italy ; Department of Biomedicine and Prevention, School of Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giardina
authors.affiliation: Fondazione Policlinico Tor Vergata, 00133 Rome, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Nardone
authors.affiliation: Fondazione Policlinico Tor Vergata, 00133 Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Postorivo
authors.affiliation: IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy ; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fornai
authors.affiliation: IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy ; Department of Biomedicine and Prevention, School of Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.affiliation: IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Romoli
authors.affiliation: IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ruggieri
authors.affiliation: IRCCS Neuromed, Località Camerelle, 86077 Pozzilli, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gambardella