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2014 ; 34
(2
): 217-24
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The neurogenetics of atypical parkinsonian disorders
#MMPMID24963681
Fogel BL
; Clark MC
; Geschwind DH
Semin Neurol
2014[Apr]; 34
(2
): 217-24
PMID24963681
show ga
Although classic Parkinson disease is the disorder most commonly associated with
the clinical feature of parkinsonism, there is in fact a broader spectrum of
disease represented by a collection of phenotypically similar neurodegenerative
conditions that mimic many of its core features. These atypical parkinsonian
disorders most commonly include progressive supranuclear palsy and corticobasal
degeneration, disorders both associated with frontotemporal dementia, as well as
multiple system atrophy and dementia with Lewy bodies. Although the clinical
distinction of these disorders still remains a challenge to physicians, recent
advances in genetics are poised to tease apart the differences. Insights into the
molecular etiologies underlying these conditions will improve diagnosis, yield a
better understanding of the underlying disease pathology, and ultimately lend
stimulation to the development of potential treatments. At the same time, the
wide range of phenotypes observed from mutations in a single gene warrants broad
testing facilitated by advances in DNA sequencing. These expanding genomic
approaches, ranging from the use of next-generation sequencing to identify
causative or risk-associated gene variations to the study of epigenetic
modification linking human genetics to environmental factors, are poised to lead
the field into a new age of discovery.