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@ARTICLE{Giordano:139488,
author = {Giordano, Ilaria and Harmuth, Florian and Jacobi, Heike and
Paap, Brigitte and Vielhaber, Stefan and Machts, Judith and
Schöls, Ludger and Synofzik, Matthis and Sturm, Marc and
Tallaksen, Chantal and Wedding, Iselin M and Boesch, Sylvia
and Eigentler, Andreas and van de Warrenburg, Bart and van
Gaalen, Judith and Kamm, Christoph and Dudesek, Ales and
Kang, Jun-Suk and Timmann, Dagmar and Silvestri, Gabriella
and Masciullo, Marcella and Klopstock, Thomas and Neuhofer,
Christiane and Ganos, Christos and Filla, Alessandro and
Bauer, Peter and Tezenas du Montcel, Sophie and Klockgether,
Thomas},
title = {{C}linical and genetic characteristics of sporadic
adult-onset degenerative ataxia.},
journal = {Neurology},
volume = {89},
number = {10},
issn = {0028-3878},
address = {[S.l.]},
publisher = {Ovid},
reportid = {DZNE-2020-05810},
pages = {1043-1049},
year = {2017},
abstract = {To define the clinical phenotype and natural history of
sporadic adult-onset degenerative ataxia and to identify
putative disease-causing mutations.Methods:The primary
measure of disease severity was the Scale for the Assessment
and Rating of Ataxia (SARA). DNA samples were screened for
mutations using a high-coverage ataxia-specific gene panel
in combination with next-generation sequencing.Results:The
analysis was performed on 249 participants. Among them, 83
met diagnostic criteria of clinically probable multiple
system atrophy cerebellar type (MSA-C) at baseline and
another 12 during follow-up. Positive MSA-C criteria (4.94
± 0.74, p < 0.0001) and disease duration (0.22 ± 0.06 per
additional year, p = 0.0007) were associated with a higher
SARA score. Forty-eight participants who did not fulfill
MSA-C criteria and had a disease duration of >10 years were
designated sporadic adult-onset ataxia of unknown
etiology/non-MSA (SAOA/non-MSA). Compared with MSA-C,
SAOA/non-MSA patients had lower SARA scores (13.6 ± 6.0 vs
16.0 ± 5.8, p = 0.0200) and a slower annual SARA increase
(1.1 ± 2.3 vs 3.3 ± 3.2, p = 0.0013). In 11 of 194 tested
participants $(6\%),$ a definitive or probable genetic
diagnosis was made.Conclusions:Our study provides
quantitative data on the clinical phenotype and progression
of sporadic ataxia with adult onset. Screening for causative
mutations with a gene panel approach yielded a genetic
diagnosis in $6\%$ of the cohort.},
keywords = {Aged / Ataxia: genetics / Ataxia: physiopathology / DNA
Mutational Analysis / Europe / Female / Follow-Up Studies /
Humans / Male / Middle Aged / Mutation / Neurodegenerative
Diseases: genetics / Neurodegenerative Diseases:
physiopathology / Severity of Illness Index},
cin = {Patient Studies Bonn / AG Düzel / AG Speck / AG Schöls /
AG Gasser / AG Levin / Magdeburg common},
ddc = {610},
cid = {I:(DE-2719)1011101 / I:(DE-2719)5000006 /
I:(DE-2719)1340009 / I:(DE-2719)5000005 / I:(DE-2719)1210000
/ I:(DE-2719)1111016 / I:(DE-2719)6000015},
pnm = {345 - Population Studies and Genetics (POF3-345) / 344 -
Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-345 / G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28794257},
doi = {10.1212/WNL.0000000000004311},
url = {https://pub.dzne.de/record/139488},
}