Format

Send to

Choose Destination
See comment in PubMed Commons below
Neurobiol Aging. 2014 Sep;35(9):2180.e1-5. doi: 10.1016/j.neurobiolaging.2014.03.024. Epub 2014 Mar 26.

Novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology.

Author information

1
Folkhälsan Institute of Genetics, Biomedicum Helsinki, Finland; Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
2
Folkhälsan Institute of Genetics, Biomedicum Helsinki, Finland; Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland. Electronic address: liisa.myllykangas@helsinki.fi.
3
Department of Medical Biochemistry and Genetics, University of Turku, Turku, Finland.
4
Department of Pathology, University of Helsinki and HUSLAB, Helsinki, Finland.
5
Department of Neurology, University of Helsinki and University Central Hospital, Helsinki, Finland.
6
Department of Neurology, University of Helsinki and University Central Hospital, Helsinki, Finland; Molecular Neurology, Research Programs Unit, Biomedicum, University of Helsinki, Helsinki, Finland.
7
Folkhälsan Institute of Genetics, Biomedicum Helsinki, Finland; Department of Clinical Genetics, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland; Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.

Abstract

We describe the clinical, neuropathological, and genetic features of a Finnish patient with a novel α-synuclein (SNCA) mutation A53E. The patient was clinically diagnosed with atypical Parkinson's disease (PD) with age of onset at 36 years. In the neuropathological analysis performed at the age of 60 years, highly abundant SNCA pathology was observed throughout the brain and spinal cord showing features of multiple system atrophy and PD. Neuronal and glial (including oligodendroglial) SNCA inclusions and neurites were found to be particularly prominent in the putamen, caudatus, amygdala, temporal and insular cortices, gyrus cinguli, and hippocampus CA2-3 region. These areas as well as the substantia nigra and locus coeruleus showed neuronal loss and gliosis. We also found TDP-43 positive but mostly SNCA negative perinuclear inclusions in the dentate fascia of the hippocampus. The A53E mutation was found in 2 other relatives who had parkinsonism. Our results suggest that the novel SNCA A53E substitution is a causative mutation resulting clinically in parkinsonism and pathologically in severe multiple system atrophy- and PD-type phenotype.

KEYWORDS:

A53E; Genetics; Neuropathology; Parkinsonism; SNCA; Synucleinopathy

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center