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

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. © 2015 rosangela ferese et al.