18 research outputs found
Origin of the mutations in the parkin gene in Europe: exon rearrangements are independent recurrent events, whereas point mutations may result from founder effects.
Diagnostic value of asymmetric striatal D2 receptor upregulation in Parkinson's disease: an [123I]IBZM and [123I]FP-CIT SPECT study.
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51914.pdf (publisher's version ) (Closed access)INTRODUCTION: Striatal postsynaptic D2 receptors in Parkinson's disease (PD) are thought to be upregulated in the first years of the disease, especially contralateral to the clinically most affected side. The aim of this study was to evaluate whether the highest striatal D2 binding is found contralateral to the most affected side in PD, and whether this upregulation can be used as a diagnostic tool. METHODS: Cross-sectional survey was undertaken of 81 patients with clinically asymmetric PD, without antiparkinsonian drugs and with a disease duration of < or = 5 years and 26 age-matched controls. Striatal D2 binding was assessed with [123I]IBZM SPECT, and severity of the presynaptic dopaminergic lesion with [123I]FP-CIT SPECT. RESULTS: The mean striato-occipital ratio of [123I]IBZM binding was significantly higher in PD patients (1.56 +/-0.09) than in controls (1.53 +/-0.06). In PD patients, higher values were found contralateral to the clinically most affected side (1.57 +/-0.09 vs 1.55 +/-0.10 ipsilaterally), suggesting D2 receptor upregulation, and the reverse was seen using [123I]FP-CIT SPECT. However, on an individual basis only 56% of PD patients showed this upregulation. CONCLUSION: Our study confirms asymmetric D2 receptor upregulation in PD. However, the sensitivity of contralateral higher striatal [123I]IBZM binding is only 56%. Therefore, the presence of contralateral higher striatal IBZM binding has insufficient diagnostic accuracy for PD, and PD cannot be excluded in patients with parkinsonism and no contralateral upregulation of D2 receptors, assessed with [123I]IBZM SPECT
Oestrogen Regulates the Expression and Function of Dopamine Transporters in Astrocytes of the Nigrostriatal System
Evaluation of oral conditions in patients with neurodegenerative diseases treated in geriatric centers
New parkin mutations and atypical phenotypes in families with autosomal recessive parkinsonism.
The frequency of parkin mutations was evaluated in 30 families of highly diverse geographic origin with early-onset autosomal recessive parkinsonism. Twelve different mutations, six of which were new, were found in 10 families from Europe and Brazil. Patients with parkin mutations had significantly longer disease duration than patients without the mutation but with similar severity of disease, suggesting a slower disease course. Two patients with parkin mutations had atypical clinical presentation at onset, with predominant tremor when standing
ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease
Objective: To assess the prevalence, nature, and associated phenotypes of ATP13A2
gene mutations among patients with juvenile parkinsonism (onset21 years) or young onset (between
21 and 40 years) Parkinson disease (YOPD). Methods: We studied 46 patients, mostly from Italy or
Brazil, including 11 with juvenile parkinsonism and 35 with YOPD. Thirty-three cases were sporadic
and 13 had positive family history compatible with autosomal recessive inheritance. Forty-two had
only parkinsonian signs, while four (all juvenile-onset) had multisystemic involvement. The whole
ATP13A2 coding region (29 exons) and exon-intron boundaries were sequenced from genomic DNA.
Results: A novel homozygous missense mutation (Gly504Arg) was identified in one sporadic case from
Brazil with juvenile parkinsonism. This patient had symptoms onset at age 12, levodopa-responsive
severe akinetic-rigid parkinsonism, levodopa-induced motor fluctuations and dyskinesias, severe visual
hallucinations, and supranuclear vertical gaze paresis, but no pyramidal deficit nor dementia.
Brain CT scan showed moderate diffuse atrophy. Furthermore, two Italian cases with YOPD without
atypical features carried a novel missense mutation (Thr12Met, Gly533Arg) in single heterozygous
state. Conclusions: We confirm that ATP13A2 homozygous mutations are associated with human
parkinsonism, and expand the associated genotypic and clinical spectrum, by describing a homozygous
missense mutation in this gene in a patient with a phenotype milder than that initially associated
with ATP13A2 mutations (Kufor-Rakeb syndrome). Our data also suggest that ATP13A2 single heterozygous
mutations might be etiologically relevant for patients with YOPD and further studies of this
gene in Parkinson disease are warranted