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

Antonio E. Elia, Simona Petrucci, Alfonso Fasano, Marco Guidi, Stefano Valbonesi, Laura Bernardini, Federica Consoli, Alessandro Ferraris, Alberto Albanese, Enza Maria Valente

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)813-817
Number of pages5
JournalMovement Disorders
Volume28
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Alpha-synuclein
  • Deep brain stimulation
  • Gene duplication
  • Parkinson's disease
  • SNCA

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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