A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction.
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.
Puschmann
Andreas
A
Department of Neurology, Lund University Hospital, Sweden; Department of Clinical Science, Section of Geriatric Psychiatry, Lund University, Sweden. andreas.puschmann@med.lu.se
Ross
Owen A
OA
Vilariño-Güell
Carles
C
Lincoln
Sarah J
SJ
Kachergus
Jennifer M
JM
Cobb
Stephanie A
SA
Lindquist
Suzanne G
SG
Nielsen
Jørgen E
JE
Wszolek
Zbigniew K
ZK
Farrer
Matthew
M
Widner
Håkan
H
van Westen
Danielle
D
Hägerström
Douglas
D
Markopoulou
Katerina
K
Chase
Bruce A
BA
Nilsson
Karin
K
Reimer
Jan
J
Nilsson
Christer
C
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
D007381:Intermediate Filament Proteins; C430456:desmuslin