TY - JOUR
T1 - Comparison of Kindreds with Parkinsonism and α-Synuclein Genomic Multiplications
AU - Farrer, Matt
AU - Kachergus, Jennifer
AU - Forno, Lysia
AU - Lincoln, Sarah
AU - Wang, Deng Shun
AU - Hulihan, Mary
AU - Maraganore, Demetrius
AU - Gwinn-Hardy, Katrina
AU - Wszolek, Zbigniew
AU - Dickson, Dennis
AU - Langston, J. William
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/2
Y1 - 2004/2
N2 - Genomic triplication of the α-synuclein gene recently has been associated with familial Parkinson's disease in the Spellman-Muenter kindred. Here, we present an independent family, of Swedish-American descent, with hereditary early-onset parkinsonism with dementia due to α-synuclein triplication. Brain tissue available from affected individuals in both kindreds provided the opportunity to compare their clinical, pathological, and biochemical phenotypes. Of note, studies of brain mRNA and soluble protein levels demonstrate a doubling of α-synuclein expression, consistent with molecular genetic data. Pathologically, cornu ammonis 2/3 hippocampal neuronal loss appears to be a defining feature of this form of inherited parkinsonism. The profound implications of α-synuclein overexpression for idiopathic synucleinopathies are discussed.
AB - Genomic triplication of the α-synuclein gene recently has been associated with familial Parkinson's disease in the Spellman-Muenter kindred. Here, we present an independent family, of Swedish-American descent, with hereditary early-onset parkinsonism with dementia due to α-synuclein triplication. Brain tissue available from affected individuals in both kindreds provided the opportunity to compare their clinical, pathological, and biochemical phenotypes. Of note, studies of brain mRNA and soluble protein levels demonstrate a doubling of α-synuclein expression, consistent with molecular genetic data. Pathologically, cornu ammonis 2/3 hippocampal neuronal loss appears to be a defining feature of this form of inherited parkinsonism. The profound implications of α-synuclein overexpression for idiopathic synucleinopathies are discussed.
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U2 - 10.1002/ana.10846
DO - 10.1002/ana.10846
M3 - Article
C2 - 14755720
AN - SCOPUS:10744227740
SN - 0364-5134
VL - 55
SP - 174
EP - 179
JO - Annals of neurology
JF - Annals of neurology
IS - 2
ER -