title: A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction.
abstract: 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.
authors.affiliation: Department of Neurology, Lund University Hospital, Sweden; Department of Clinical Science, Section of Geriatric Psychiatry, Lund University, Sweden. andreas.puschmann@med.lu.se
authors.forename: Andreas
authors.initials: A
authors.lastname: Puschmann
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: Carles
authors.initials: C
authors.lastname: Vilariño-Güell
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lincoln
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Kachergus
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Cobb
authors.forename: Suzanne G
authors.initials: SG
authors.lastname: Lindquist
authors.forename: Jørgen E
authors.initials: JE
authors.lastname: Nielsen
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Matthew
authors.initials: M
authors.lastname: Farrer
authors.forename: Håkan
authors.initials: H
authors.lastname: Widner
authors.forename: Danielle
authors.initials: D
authors.lastname: van Westen
authors.forename: Douglas
authors.initials: D
authors.lastname: Hägerström
authors.forename: Katerina
authors.initials: K
authors.lastname: Markopoulou
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Chase
authors.forename: Karin
authors.initials: K
authors.lastname: Nilsson
authors.forename: Jan
authors.initials: J
authors.lastname: Reimer
authors.forename: Christer
authors.initials: C
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013548:Sweden
chemical_list: D007381:Intermediate Filament Proteins; C430456:desmuslin