Publications (2)16.62 Total impact
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Article: Hyposmia in G2019S LRRK2-related parkinsonism: clinical and pathologic data.
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ABSTRACT: Mutations in PARK8 (LRRK2) are associated with autosomal dominant parkinsonism and Parkinson disease (PD). Hyposmia is present in at least 80% of patients with PD and an accumulation of alpha-synuclein (alpha-syn) is seen in the olfactory pathways. In this study we have clinically examined olfaction and pathologically examined the rhinencephalon in individuals carrying the G2019S LRRK2 mutation. The University of Pennsylvania Smell Test (UPSIT) was used to evaluate the sense of smell in 19 parkinsonian and two asymptomatic carriers of the G2019S mutation and compared with groups of patients with PD and healthy controls. Postmortem examination of alpha-syn accumulation in the rhinencephalon was also carried out in four parkinsonian carriers of the G2019S mutation. The mean UPSIT score in G2019S parkinsonian carriers was lower than that in healthy controls (p < 0.001) and similar to that found in patients with PD (p > 0.999). Smell tests in two asymptomatic carriers of the G2019S mutation were in the normal range. Postmortem studies of the olfactory pathways in one of the patients who had been clinically tested, and found to have hyposmia, and three other cases with the G2019S mutation, revealed alpha-syn deposition in the olfactory pathways in all cases. Odor identification is diminished in LRRK2 G2019S mutation parkinsonism but the asymptomatic carriers of the mutation had normal olfaction. We found alpha-syn accumulation with Lewy bodies in the rhinencephalon in all four cases examined pathologically.Neurology 09/2008; 71(13):1021-6. · 8.31 Impact Factor -
Article: ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease.
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ABSTRACT: To assess the prevalence, nature, and associated phenotypes of ATP13A2 gene mutations among patients with juvenile parkinsonism (onset <21 years) or young onset (between 21 and 40 years) Parkinson disease (YOPD). 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. 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. 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.Neurology 05/2007; 68(19):1557-62. · 8.31 Impact Factor
