http://repub.eur.nl/res/aut/1659/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/28054/ 2010-07-15T00:00:00Z The combination of recessive early-onset parkinsonism and pyramidal tract signs caused by pallidopyramidal degeneration is known as pallidopyramidal disease or syndrome (PPD/S). We investigated whether patients diagnosed as Davison's PPD/S showed any definite proof of pyramidal and pallidal involvement, without findings suggestive of other nosological entities. Since Davison's original description, 15 other PPD/S cases have been reported, yet all lack proof of pyramidal or pallidal degeneration. Because of the doparesponsiveness in all patients subsequent to Davison's report, we argue that these patients probably suffered from early-onset nigral parkinsonism or dopa-responsive dsystonia, rather than pallidal parkinsonism; in such cases, the presumed pyramidal Babinski could be a pseudobabinski ("striatal toe"). Secondary pallidopyramidal syndromes do occur, for example, in multiple system atrophy or Wilson's disease, but in these patients additional findings indicate diseases other than Davison's PPD/S. We conclude that the existence of PPD/S as a distinct clinico-pathological nosological entity, as proposed by Davison, is doubtful. In cases reported as Davison's PPD/S, the description "pallidopyramidal" seems to be a misnomer. http://repub.eur.nl/res/pub/24490/ 2009-11-05T00:00:00Z Mutations in the Grb10-interacting GYF protein 2 (GIGYF2) gene, within the PARK11 locus, have been nominated as a cause of Parkinson's disease in Italian and French populations. By sequencing the whole GIGYF2 coding region in forty-six probands (thirty-seven Italians) with familial Parkinson's disease compatible with an autosomal dominant inheritance, we identified no mutations. Our data add to a growing body of evidence suggesting that GIGYF2 mutations are not a frequent cause of PD. http://repub.eur.nl/res/pub/5905/ 2003-07-01T00:00:00Z We recently reported linkage to chromosome 1p36 (the PARK7-locus) in a family with early-onset parkinsonism. Linkage to this locus has since been confirmed in an independent data set. We describe clinical and neuroimaging features of the 4 patients in the original PARK7-linked kindred. Age at onset of parkinsonism varied from 27 to 40 years. Clinical progression was slow, and response to dopaminergic therapy good. The clinical spectrum ranged from mild hypokinesia and rigidity, to severe parkinsonism with levodopa-induced dyskinesias and motor fluctuation. Three of four patients with PARK7-linked parkinsonism exhibited psychiatric disturbances. Structural neuroimaging was unremarkable, but functional imaging of the brain, carried out in 3 patients, showed significant evidence for a presynaptic dopamine deficit, and assessment of cerebral glucose metabolism, as carried out in 1 patient, showed possible cerebellar involvement. http://repub.eur.nl/res/pub/8482/ 2001-01-01T00:00:00Z Although the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Parkin gene, and recently a second gene, PARK6, involved in early-onset recessive parkinsonism was localized on chromosome 1p35-36. We identified a family segregating early-onset parkinsonism with multiple consanguinity loops in a genetically isolated population. Homozygosity mapping resulted in significant evidence for linkage on chromosome 1p36. Multipoint linkage analysis using MAPMAKER-HOMOZ generated a maximum LOD-score of 4.3, with nine markers spanning a disease haplotype of 16 cM. On the basis of several recombination events, the region defining the disease haplotype can be clearly separated, by > or =25 cM, from the more centromeric PARK6 locus on chromosome 1p35-36. Therefore, we conclude that we have identified on chromosome 1 a second locus, PARK7, involved in autosomal recessive, early-onset parkinsonism.