A Swedish family with de novo α-synuclein A53T mutation: Evidence for early cortical dysfunction

Andreas Puschmann, Owen A. Ross, Carles Vilariño-Güell, Sarah J. Lincoln, Jennifer M. Kachergus, Stephanie A. Cobb, Suzanne G. Lindquist, Jørgen E. Nielsen, Zbigniew K. Wszolek, Matthew Farrer, Håkan Widner, Danielle van Westen, Douglas Hägerström, Katerina Markopoulou, Bruce A. Chase, Karin Nilsson, Jan Reimer, Christer Nilsson

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


A de novo α-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G > A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected, but was not associated with disease state.

Original languageEnglish (US)
Pages (from-to)627-632
Number of pages6
JournalParkinsonism and Related Disorders
Issue number9
StatePublished - Nov 5 2009
Externally publishedYes


  • A53T
  • A53T mutation
  • Ala53Thr
  • Alpha-synuclein
  • Autosomal dominant parkinsonism
  • Biomarkers
  • CSF examination
  • Cerebrospinal fluid
  • Electroencephalogram
  • Haplotype analysis
  • Longitudinal clinical follow-up
  • Magnetic resonance imaging
  • Myoclonus
  • Neuroimaging
  • Parkinson disease
  • Parkinsonian conditions
  • Single-photon emission computed tomography

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology


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