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@ARTICLE{Mol:153322,
author = {Mol, Merel O and van Rooij, Jeroen G J and Brusse, Esther
and Verkerk, Annemieke J M H and Melhem, Shamiram and den
Dunnen, Wilfred F A and Rizzu, Patrizia and Cupidi, Chiara
and van Swieten, John C and Donker Kaat, Laura},
title = {{C}linical and pathologic phenotype of a large family with
heterozygous {STUB}1 mutation.},
journal = {Neurology / Genetics},
volume = {6},
number = {3},
issn = {2376-7839},
address = {Minneapolis, Minn.},
reportid = {DZNE-2020-01319},
pages = {e417},
year = {2020},
abstract = {To describe the clinical and pathologic features of a novel
pedigree with heterozygous STUB1 mutation causing SCA48.We
report a large pedigree of Dutch decent. Clinical and
pathologic data were reviewed, and genetic analyses
(whole-exome sequencing, whole-genome sequencing, and
linkage analysis) were performed on multiple family
members.Patients presented with adult-onset gait disturbance
(ataxia or parkinsonism), combined with prominent cognitive
decline and behavioral changes. Whole-exome sequencing
identified a novel heterozygous frameshift variant
$c.731_732delGC$ (p.C244Yfs*24) in STUB1 segregating with
the disease. This variant was present in a linkage peak on
chromosome 16p13.3. Neuropathologic examination of 3 cases
revealed a consistent pattern of ubiquitin/p62-positive
neuronal inclusions in the cerebellum, neocortex, and
brainstem. In addition, tau pathology was present in 1
case.This study confirms previous findings of heterozygous
STUB1 mutations as the cause of SCA48 and highlights its
prominent cognitive involvement, besides cerebellar ataxia
and movement disorders as cardinal features. The presence of
intranuclear inclusions is a pathologic hallmark of the
disease. Future studies will provide more insight into its
pathologic heterogeneity.},
cin = {AG Rizzu},
ddc = {610},
cid = {I:(DE-2719)1210009},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32337344},
pmc = {pmc:PMC7164971},
doi = {10.1212/NXG.0000000000000417},
url = {https://pub.dzne.de/record/153322},
}