A Swedish family with de novo alpha-synuclein A53T mutation: Evidence for early cortical dysfunction
ΣυγγραφέαςPuschmann, A.; Ross, O. A.; Vilarino-Guell, C.; Lincoln, S. J.; Kachergus, J. M.; Cobb, S. A.; Lindquist, S. G.; Nielsen, J. E.; Wszolek, Z. K.; Farrer, M.; Widner, H.; van Westen, D.; Hagerstrom, D.; Markopoulou, K.; Chase, B. A.; Nilsson, K.; Reimer, J.; Nilsson, C.
A de novo alpha-symaclein 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. (C) 2009 Elsevier Ltd. All rights reserved.