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Four Copies of SNCA Responsible for Autosomal Dominant Parkinson’s Disease in Two Italian Siblings

2015; Hindawi Publishing Corporation; Volume: 2015; Linguagem: Inglês

10.1155/2015/546462

2090-8083

Rosangela Ferese, Nicola Modugno, Rosa Campopiano, Marco Santilli, Stefania Zampatti, Emiliano Giardina, A. Nardone, Diana Postorivo, Francesco Fornai, Giuseppe Novelli, Edoardo Romoli, Stefano Ruggieri, Stefano Gambardella,

Autism Spectrum Disorder Research

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.