A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction

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

A de novo alpha-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
JournalParkinsonism & Related Disorders
Issue number9
Pages (from-to)627-32
Number of pages5
Publication statusPublished - 2009

Bibliographical note

Keywords: Adult; Cerebral Cortex; Female; Humans; Intermediate Filament Proteins; Male; Mutation; Parkinson Disease; Pedigree; Polymerase Chain Reaction; Sweden

ID: 19976926