TY - JOUR
T1 - Four Copies of SNCA Responsible for Autosomal Dominant Parkinson's Disease in Two Italian Siblings
AU - Ferese, Rosangela
AU - Modugno, Nicola
AU - Campopiano, Rosa
AU - Santilli, Marco
AU - Zampatti, Stefania
AU - Giardina, Emiliano
AU - Nardone, Annamaria
AU - Postorivo, Diana
AU - Fornai, Francesco
AU - Novelli, Giuseppe
AU - Romoli, Edoardo
AU - Ruggieri, Stefano
AU - Gambardella, Stefano
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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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U2 - 10.1155/2015/546462
DO - 10.1155/2015/546462
M3 - Article
AN - SCOPUS:84948411377
VL - 2015
JO - npj Parkinson's Disease
JF - npj Parkinson's Disease
SN - 2090-8083
M1 - 546462
ER -