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@ARTICLE{Synofzik:136699,
author = {Synofzik, Matthis and Srulijes, Karin and Godau, Jana and
Berg, Daniela and Schöls, Ludger},
title = {{C}haracterizing {POLG} ataxia: clinics, electrophysiology
and imaging.},
journal = {The Cerebellum},
volume = {11},
number = {4},
issn = {1473-4222},
address = {London},
publisher = {Dunitz},
reportid = {DZNE-2020-03021},
pages = {1002-1011},
year = {2012},
abstract = {Mutations in the mitochondrial DNA polymerase gamma (POLG)
cause a highly pleomorphic disease spectrum, and reports
about their frequencies in ataxia populations yield
equivocal results. This leads to uncertainties about the
role of POLG genetics in the workup of patients with
unexplained ataxia. A comprehensive characterization of
POLG-associated ataxia (POLG-A) will help guide genetic
diagnostics and advance our understanding of the disease
processes underlying POLG-A. Thirteen patients with POLG-A
were assessed by standardized clinical investigation, nerve
conduction studies, motor-evoked potentials, magnetic
resonance imaging (MRI) and transcranial sonography (TCS).
The findings were compared with 13 matched patients with
Friedreich's ataxia (FA). In addition to the well-known
POLG-associated features of chronic external ophthalmoplegia
(100 $\%),$ areflexia to the lower extremity (100 $\%),$
impaired vibration sense (100 $\%),$ bilateral ptosis (69
$\%)$ and epilepsy (38 $\%),$ also hyperkinetic movement
disorders were frequent in POLG-A patients, including chorea
(31 $\%),$ dystonia (31 $\%)$ and myoclonus (23 $\%).$
Similar to FA, polyneuropathy was of sensory axonal type
(100 $\%).$ In contrast to FA, none of the POLG-A patients
showed impaired central motor conduction. TCS demonstrated
less enlargement of the fourth ventricle and more diffuse
cerebellar hyperechogenicity in POLG-A. Corresponding to
TCS, MRI revealed no or only mild cerebellar atrophy in most
POLG-A patients (85 $\%).$ POLG ataxia presents with the
clinical characteristics of both afferent and cerebellar
ataxia. Cerebellar alterations diffusely involve various
parts of the cerebellum, yet cerebellar atrophy is generally
mild. POLG-A presents with a high load of distinct
non-ataxia features, namely, sensory neuropathy, external
ophthalmoplegia, ptosis, epilepsy and/or hyperkinetic
movement disorders. Involvement of the corticospinal tract,
however, is rare.},
keywords = {Adult / Brain: pathology / DNA Polymerase gamma /
DNA-Directed DNA Polymerase: genetics / DNA-Directed DNA
Polymerase: metabolism / Electromagnetic Phenomena / Female
/ Friedreich Ataxia: genetics / Friedreich Ataxia: pathology
/ Humans / Magnetic Resonance Imaging: methods / Male /
Middle Aged / Mutation: genetics / Young Adult / DNA
Polymerase gamma (NLM Chemicals) / DNA-Directed DNA
Polymerase (NLM Chemicals) / POLG protein, human (NLM
Chemicals)},
cin = {AG Schöls 1 / AG Gasser 1 / AG Berg},
ddc = {610},
cid = {I:(DE-2719)5000005 / I:(DE-2719)1210000 /
I:(DE-2719)5000055},
pnm = {345 - Population Studies and Genetics (POF3-345)},
pid = {G:(DE-HGF)POF3-345},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:22528963},
doi = {10.1007/s12311-012-0378-2},
url = {https://pub.dzne.de/record/136699},
}