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

Abstract 

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.

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