Get access

Alpha-synuclein gene duplication: Marked intrafamilial variability in two novel pedigrees

Authors


  • Funding agencies: The research leading to these results has received funding from the Italian Ministry of Health (Ricerca Corrente 2012, Ricerca Finalizzata Malattie Rare 2008) and from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 241791 (European Project on Mendelian Forms of Parkinson's Disease [MEFOPA]).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Background

Multiplications of the SNCA gene that encodes alpha-synuclein are a rare cause of autosomal dominant Parkinson's disease (PD).

Methods

Here, we describe 2 novel families in which there is autosomal dominant PD associated with SNCA duplication, and we compare the clinical features of all known patients carrying 3 or 4 SNCA copies.

Results

Affected members in family A presented with early onset PD that was variably associated with nonmotor features, such as dysautonomia, cognitive deficits, and psychiatric disturbances. In family B, the clinical presentation ranged from early onset PD-dementia with psychiatric disturbances to late onset PD with mild cognitive impairment.

Conclusions

The presence of 4 SNCA copies is associated with a rich phenotype, characterized by earlier onset of motor and nonmotor features compared with patients who bear 3 SNCA copies. The clinical spectrum associated with SNCA duplications is wide, even within a single family, suggesting a role for as yet unidentified genetic or environmental modifiers. © 2013 Movement Disorder Society

Ancillary