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

Overview

Journal Parkinsons Dis

Publisher Wiley

Date 2015 Dec 5

PMID 26635992

Citations 32

Authors

Rosangela Ferese

Nicola Modugno

Rosa Campopiano

Marco Santilli

Stefania Zampatti

Emiliano Giardina

Annamaria Nardone

Diana Postorivo

Francesco Fornai

Giuseppe Novelli

Edoardo Romoli

Stefano Ruggieri

Stefano Gambardella

Affiliations

Soon will be listed here.

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.

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