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@ARTICLE{Thal:138204,
author = {Thal, Dietmar R and Züchner, Stephan and Gierer, Stephan
and Schulte, Claudia and Schöls, Ludger and Schüle,
Rebecca and Synofzik, Matthis},
title = {{A}bnormal {P}araplegin {E}xpression in {S}wollen
{N}eurites, τ- and α-{S}ynuclein {P}athology in a {C}ase
of {H}ereditary {S}pastic {P}araplegia {SPG}7 with an
{A}la510{V}al {M}utation.},
journal = {International journal of molecular sciences},
volume = {16},
number = {10},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DZNE-2020-04526},
pages = {25050-25066},
year = {2015},
abstract = {Mutations in the SPG7 gene are the most frequent cause of
autosomal recessive hereditary spastic paraplegias and
spastic ataxias. Ala510Val is the most common SPG7 mutation,
with a frequency of up to $1\%$ in the general population.
Here we report the clinical, genetic, and neuropathological
findings in a homozygous Ala510Val SPG7 case with spastic
ataxia. Neuron loss with associated gliosis was found in the
inferior olivary nucleus, the dentate nucleus of the
cerebellum, the substantia nigra and the basal nucleus of
Meynert. Neurofilament and/or paraplegin accumulation was
observed in swollen neurites in the cerebellar and cerebral
cortex. This case also showed subcortical τ-pathology in an
unique distribution pattern largely restricted to the
brainstem. α-synuclein containing Lewy bodies (LBs) were
observed in the brainstem and the cortex, compatible with a
limbic pattern of Braak LB-Disease stage 4. Taken together,
this case shows that the spectrum of pathologies in SPG7 can
include neuron loss of the dentate nucleus and the inferior
olivary nucleus as well as neuritic pathology. The
progressive supranuclear palsy-like brainstem predominant
pattern of τ pathology and α-synuclein containing Lewy
bodies in our SPG7 cases may be either coincidental or
related to SPG7 in addition to neuron loss and neuritic
pathology.},
keywords = {ATPases Associated with Diverse Cellular Activities / Aged
/ Basal Nucleus of Meynert: pathology / Cerebellar Nuclei:
pathology / Gene Frequency: genetics / Gliosis: genetics /
Humans / Intellectual Disability: genetics / Intellectual
Disability: pathology / Lewy Bodies: pathology / Male /
Metalloendopeptidases: biosynthesis / Metalloendopeptidases:
genetics / Muscle Spasticity: genetics / Muscle Spasticity:
pathology / Neurites: metabolism / Neurofibrillary Tangles:
pathology / Neurons: pathology / Olivary Nucleus: pathology
/ Optic Atrophy: genetics / Optic Atrophy: pathology /
Spastic Paraplegia, Hereditary: genetics / Spastic
Paraplegia, Hereditary: pathology / Spinocerebellar Ataxias:
genetics / Spinocerebellar Ataxias: pathology / Substantia
Nigra: pathology / alpha-Synuclein: metabolism / tau
Proteins: metabolism / SNCA protein, human (NLM Chemicals) /
alpha-Synuclein (NLM Chemicals) / tau Proteins (NLM
Chemicals) / Metalloendopeptidases (NLM Chemicals) / SPG7
protein, human (NLM Chemicals) / ATPases Associated with
Diverse Cellular Activities (NLM Chemicals)},
cin = {AG Berg ; AG Berg / AG Schöls / AG Maetzler},
ddc = {540},
cid = {I:(DE-2719)5000055 / I:(DE-2719)5000005 /
I:(DE-2719)5000024},
pnm = {344 - Clinical and Health Care Research (POF3-344) / 345 -
Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-344 / G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26506339},
pmc = {pmc:PMC4632789},
doi = {10.3390/ijms161025050},
url = {https://pub.dzne.de/record/138204},
}