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

Abstract EN

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.