Van de Warrenburg, B. P. C. et al. Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations. Neurology 56, 555-557

Department of Neurology, University Medical Center, Nijmegen, The Netherlands.
Neurology (Impact Factor: 8.29). 03/2001; 56(4):555-7. DOI: 10.1212/WNL.56.4.555
Source: PubMed


A Dutch family with autosomal recessive early-onset parkinsonism showed a heterozygous missense mutation in combination with a heterozygous exon deletion in the parkin gene. Although the main clinical syndrome consisted of parkinsonism, the proband clinically had additional mild gait ataxia and pathologically showed neuronal loss in parts of the spinocerebellar system, in addition to selective loss of dopaminergic neurons in the substantia nigra pars compacta. Lewy bodies and neurofibrillary tangles were absent, but tau pathology was found.

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Available from: Patrice Denèfle, Dec 12, 2013
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    • "While pathological studies on genetic forms of PD are limited, it is clear that at least some of these patients do not show classic Lewy pathology. Indeed, in the case of LRRK2 mutations even within a single family, a spectrum of pathology has been observed among family members with manifesting PD, ranging from those completely lacking any synuclein pathology, to those with significant αsyn aggregation [80-84]. Furthermore a recent study comparing neuronal dysfunction in relation to Braak stage in patients with PD, individuals with ILBD and controls has demonstrated that both cellular dysfunction (loss of tyrosine hydroxylase) and neurodegeneration can precede Lewy body pathology in ILBD [73]. "
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    ABSTRACT: Parkinson’s disease (PD) is a progressive neurodegenerative disorder typified by the presence of intraneuronal inclusions containing aggregated alpha synuclein (αsyn). The progression of parkinsonian pathology and clinical phenotype has been broadly demonstrated to follow a specific pattern, most notably described by Braak and colleagues. In more recent times it has been hypothesized that αsyn itself may be a critical factor in mediating transmission of disease pathology from one brain area to another. Here we investigate the growing body of evidence demonstrating the ability of αsyn to spread transcellularly and induce pathological aggregation affecting neurons by permissive templating and provide a critical analysis of some irregularities in the hypothesis that the progression of PD pathology may be mediated by such a prion-like process. Finally we discuss some key questions that remain unanswered which are vital to determining the potential contribution of a prion-like process to the pathogenesis of PD.
    Full-text · Article · May 2013
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    • "Table 1. Pathological Reports of Published Parkin Cases Source Yamamura et al, 16 1998 Mori et al, 17 1998 Hayashi et al, 18 2000 Van de Warrenburg et al, 19 2001 Farrer et al, 20 2001 Mori et al, 21 2003 "
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    ABSTRACT: IMPORTANCE Mutations in the gene encoding parkin (PARK2) are the most common cause of autosomal recessive juvenile-onset and young-onset parkinsonism. The few available detailed neuropathologic reports suggest that homozygous and compound heterozygous parkin mutations are characterized by severe substantia nigra pars compacta neuronal loss. OBJECTIVE To investigate whether parkin -linked parkinsonism is a different clinicopathologic entity to Parkinson disease (PD). DESIGN, SETTING, AND PARTICIPANTS We describe the clinical, genetic, and neuropathologic findings of 5 unrelated cases of parkin disease and compare them with 5 pathologically confirmed PD cases and 4 control subjects. The PD control cases and normal control subjects were matched first for age at death then disease duration (PD only) for comparison. RESULTS Presenting signs in the parkin disease cases were hand or leg tremor often combined with dystonia. Mean age at onset was 34 years; all cases were compound heterozygous for mutations of parkin. Freezing of gait, postural deformity, and motor fluctuations were common late features. No patients had any evidence of cognitive impairment or dementia. Neuronal counts in the substantia nigra pars compacta revealed that neuronal loss in the parkin cases was as severe as that seen in PD, but relative preservation of the dorsal tier was seen in comparison with PD (P = .04). Mild neuronal loss was identified in the locus coeruleus and dorsal motor nucleus of the vagus, but not in the nucleus basalis of Meynert, raphe nucleus, or other brain regions. Sparse Lewy bodies were identified in 2 cases (brainstem and cortex). CONCLUSIONS AND RELEVANCE These findings support the notion that parkin disease is characterized by a more restricted morphologic abnormality than is found in PD, with predominantly ventral nigral degeneration and absent or rare Lewy bodies.
    Full-text · Article · Mar 2013
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    • "Pathology in patients with Parkin mutation may show a different pattern than that in idiopathic PD. For instance, tau accumulation has been demonstrated in the basal ganglia of such patients but not in the idiopathic cases [28]. The type of the mutation may also have an important impact on the findings: many of the PD-linked point mutations, identified in only 2 out of 9 YOPD-p patients in our study, produce alterations in the solubility and intracellular localization of the wild-type Parkin where the mutation mediated-alteration in Parkin solubility is associated with "
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    ABSTRACT: Parkin (PARK2) gene mutations are the predominant cause of autosomal recessive parkinsonism. Characteristic features include: early onset symptoms with slow clinical course, good response to low doses of levodopa, and frequently treatment-induced dyskinesia. Studies using a voxel-based morphometry approach showed a decrease in the gray matter volume of the basal ganglia in mutation carriers during the symptomatic stages. A bilateral, presumably compensatory increase of basal ganglia gray matter value was recently demonstrated in asymptomatic Parkin mutation carriers. Behavioral disorders including: anxiety, psychosis, panic attacks, depression, disturbed sexual, behavioral and obsessive-compulsive disorders have been reported in these patients. A total of 28 Parkinson's Disease (PD) patients consisting of 10 Young-Onset without Parkin mutations (YOPD), 9 Young-Onset with Parkin mutations (YOPD-p), 9 Late-Onset without Parkin mutations (LOPD) and 32 healthy control subjects were studied with an automated volumetric assessment method to quantify subcortical atrophy. Patients but not controls also underwent a neuropsychological and neuropsychiatric assessment. Results revealed a reduction of bilateral caudate nuclei volumes in YOPD-p patients compared to the YOPD patients while there were no statistically significant differences between other groups. YOPD-p patients showed similar results to other patient groups on neuropsychiatric and neuropsychological evaluation measures. YOPD-p and YOPD patients showed a different pattern of volume changes in basal ganglia. Despite its relatively benign clinical course, carrying the Parkin mutation seems to be associated with greater atrophy in subcortical structures. Failure of compensatory mechanisms, different mutation types and pathophysiologic processes may underlie this diverse pattern of subcortical brain changes.
    Full-text · Article · Mar 2012 · Parkinsonism & Related Disorders
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