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

作者：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

来源：Parkinsons Disease, 2015, 2015: 546462.

DOI：10.1155/2015/546462

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 1,29Mb 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.

• 出版日期2015