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Zbigniew K Wszolek

Publications and source records attributed to Zbigniew K Wszolek.

At least 55 records · Page 3Linked to original sources
PubMed2005

Sporadic SCA8 mutation resembling corticobasal degeneration.

Spinocerebellar ataxia type 8 (SCA8) is caused by the expansion of CTA/CTG triplet repeats on 13q21. Cases can be familial or sporadic. The clinical findings include cerebellar ataxia with upper motor neuron dysfunction, dysphagia, peripheral sensory disturbances, or cognitive and psychiatric impairments, indicating phenotypic variability in SCA8. We report on a patient with rapidly progressive parkinsonism-plus syndrome resembling corticobasal degeneration and triplet expansions in the SCA8 locus. The relationship between clinical phenotype and triplet expansions in the SCA8 locus requires further study.

Aged↗
PubMed2005

The effect of tau genotype on clinical features in FTDP-17.

The clinical phenotype of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) varies. This variability is seen not only between kindreds with different mutations but also in families sharing the same mutation. Inheritance of tau haplotype (H1) and genotype (H1/H1) has been established as a risk factor for some neurodegenerative disorders with parkinsonism. We assessed the effect of tau polymorphism on the clinical features of FTDP-17 in 61 cases from 30 separately ascertained families with four different tau mutations, including P301L, +16, N279K, and P301S. There were no significant differences of age at symptomatic onset and disease duration between H1/H1 and H1/H2 genotypes. The comparison between tau genotype and type of initial clinical sign showed an association between the H1/H1 genotype and parkinsonian phenotype and between the H1/H2 genotype and frontotemporal dementia phenotype (OR=11.7; 95% confidence interval, 1.4-98.7; P=0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17.

Adult↗
PubMed2005

Heredofamilial brain calcinosis syndrome.

Brain calcinosis syndrome (BCS) usually is defined as bilateral calcium accumulation in the brain parenchyma, primarily in the basal ganglia. More than 50 reported clinical conditions have been associated with BCS. We reviewed clinical, radiological, and genetic features of heredofamilial BCS accompanying all conditions associated with calcium accumulation in the brain reported in English between 1962 and 2003 in MEDLINE. The location, extent, and degree of calcification in the brain show diversity not only among the various disorders but also among patients sharing the same condition. The pathogenesis of BCS is uncertain. More complicated mechanisms may be Involved when brain calcinosis is present but calcium, phosphorus, and parathyroid hormone metabolism abnormalities are absent. We review conditions associated with heredofamilial BCS in which brain calcinosis is nearly uniformly present because such information may be Important to the clinician pursuing an investigative strategy.

Basal Ganglia Diseases↗
PubMed2004

Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology.

We have previously linked families with autosomal-dominant, late-onset parkinsonism to chromosome 12p11.2-q13.1 (PARK8). By high-resolution recombination mapping and candidate gene sequencing in 46 families, we have found six disease-segregating mutations (five missense and one putative splice site mutation) in a gene encoding a large, multifunctional protein, LRRK2 (leucine-rich repeat kinase 2). It belongs to the ROCO protein family and includes a protein kinase domain of the MAPKKK class and several other major functional domains. Within affected carriers of families A and D, six post mortem diagnoses reveal brainstem dopaminergic degeneration accompanied by strikingly diverse pathologies. These include abnormalities consistent with Lewy body Parkinson's disease, diffuse Lewy body disease, nigral degeneration without distinctive histopathology, and progressive supranuclear palsy-like pathology. Clinical diagnoses of Parkinsonism with dementia or amyotrophy or both, with their associated pathologies, are also noted. Hence, LRRK2 may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism.

Adult↗
PubMed2004

Profile of families with parkinsonism-predominant spinocerebellar ataxia type 2 (SCA2).

Spinocerebellar ataxia type 2 (SCA2) has been recognized recently as an uncommon cause of parkinsonism, an alternate presentation to the typical cerebellar disorder. This research review summarizes the existing literature on parkinsonism-predominant presentation SCA2 and presents new clinical cases of patients with this condition. Various phenotypes are noted in this subtype of SCA2, including parkinsonism indistinguishable from idiopathic Parkinson's disease (PD), parkinsonism plus ataxia, motor neuron disease, and postural tremor. In several kindreds with multiple affected family members, the SCA2 expansion segregated with disease; in addition, several single cases of parkinsonism with and without a family history are also described. The number of repeats in symptomatic patients ranged from 33 to 43. Interruption of the CAG repeat with CAA, CGG, or CCG was found in some individuals, possibly stabilizing the repeat structure and accounting for the relative stability of the repeat size across generations in some families; allele length is not necessarily indicative of trinucleotide repeat architecture. Positron emission tomography scanning in one family showed reduced fluorodopa uptake and normal to increased raclopride binding with a rostrocaudal gradient similar to that found in idiopathic PD. This review emphasizes the importance of testing for SCA2 in patients with parkinsonism and a family history of neurodegenerative disorders. Testing for SCA2 is also important in studies of inherited parkinsonism.

Antiparkinson Agents↗
PubMed2004

Is the neuropathological 'gold standard' diagnosis dead? Implications of clinicopathological findings in an autosomal dominant neurodegenerative disorder.

Genetically-derived neurodegenerative disorders offer a rare opportunity to test validity of neuropathological criteria for diagnosis. Implications regarding an autosomal dominant neurodegenerative disorder (PARK 8) in which four different neuropathological diagnoses were found at autopsy are discussed. We suggest that just as there is currently no clinical 'gold standard' for Parkinson's disease, there is no pathological 'gold standard.' We conclude that in certain circumstances genetic studies may provide definitive arbitration of validity of clinical and pathological diagnostic criteria.

Heredodegenerative Disorders, Nervous System↗
PubMed2003

Clinical-electrophysiological correlation of tremor and myoclonus in a kindred with the N279K tau mutation.

We used electrophysiological methods to study the hyperkinetic movement disorders in a pallido-ponto-nigral degeneration (PPND) family, which harbors the N279K tau gene mutation. Our purpose was to: (1). characterize the tremor patterns, (2). characterize the myoclonus physiology, (3). determine whether electrophysiology can detect abnormalities in asymptomatic cases. In PPND, we found that the activation tremors correlated with a semi-rhythmic 6-10 Hz electromyography (EMG) pattern, and the rest tremors showed a reciprocal 4-6 Hz pattern. At least two different myoclonus physiology patterns exist in PPND, most notably contrasted by the presence or absence of a demonstrable electroencephalography (EEG) correlate. Electrophysiology yielded remarkable findings in those asymptomatic at-risk individuals that carried the N279K tau mutation.

Electromyography↗
PubMed2003

Two large Polish kindreds with levodopa-responsive Parkinsonism not linked to known Parkinsonian genes and loci.

PURPOSE: We describe two newly discovered large Polish families with Parkinsonism, PL-Krakow 1 and PL-Krakow 2. SCOPE: As illustrated by case reports from two patients, the disease phenotype is similar to that seen in patients with idiopathic Parkinson's disease, and affected individuals show a positive response to levodopa therapy. Molecular genetic studies failed to demonstrate a single chromosomal haplotype that segregated with disease for any of the known loci for Parkinsonism. CONCLUSIONS: The study of large kindreds such as this provides opportunities to find new Parkinsonian loci and mutations. This knowledge will help to better our understanding of the basic mechanisms leading to the degeneration of vulnerable substantia nigra neurons and other susceptible brain structures.

Activities of Daily Living↗
PubMed2003

[Japanese contribution to the understanding of frontotemporal dementia and parkinsonism linked to chromosome 17(FTDP-17)].

Since the original description of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) during the Consensus Conference held in Ann Arbor, Michigan in 1996, it has become apparent that this syndrome has worldwide distribution. More than 70 families have been described in North America, Europe, Australia and Asia. The molecular genetic studies have identified 29 mutations outside and on exon 10 of tau gene. Here, we report the progress in clinical, genetic and pathological studies of FTDP-17 in Japan. There have been 15-separetely ascertained families described in Japan. These kindreds harbor following tau mutations: exon 10, exonic mutations, N 279 K, N 296 H, P 301 L and P 301 S; exon 10 5' splice-site mutations, S 305 N (-2), +11, and +12; exon 1, R 5 H mutation; exon 9, L 266 V mutation; and exon 13, R 406 W mutation. The phenotype of FTDP-17 kindreds varies significantly between families with different mutations and among the families carrying the same mutation. This variability is also seen in Japanese kindreds. Exon 10, P 301 L, +16 and N 279 K mutations are the most common but only P 301 L and N 279 K mutations have been described so far in Japan. On the other hand, R 5 H, N 296 H, +11, and +12 mutations have not been identified outside of Japan. Comparison of phenotypes of Japanese and non-Japanese families with P 301 S, P 301 L and R 406 W mutations uncovers significant differences in clinical presentations. It is difficult to compare pathology of Japanese and non-Japanese families on the basis of available medical literature but no apparent differences can be seen. Autopsies demonstrate the presence of neuronal and glial tau inclusions and ballooned neurons, frequently in the distribution seen in other sporadic tauopathies. A search for the common founder in Japanese families may be successfully performed. FTDP-17 families have been identified with increasing frequency in Japan. The discovery of tau mutations and the fact that they are responsible for the disease processes in the brain lead to the major advancement of our understanding of neurodegeneration. It is hoped that future studies of these families will also lead to finding the curative treatments for the tauopathies.

Chromosomes, Human, Pair 17↗
PubMed2002

Physiologic assessment of autonomic dysfunction in pallidopontonigral degeneration with N279K mutation in the tau gene on chromosome 17.

Autonomic function was investigated in five affected and five at-risk members of a single kinship of pallidopontonigral degeneration (PPND), which is a progressive syndrome of parkinsonism and frontotemporal dementia resulting from a mutation in the N279K tau gene on chromosome 17. Affected subjects reported symptoms including hyperhidrosis, sialorrhea, urinary frequency or incontinence, thermal intolerance, male sexual dysfunction, lacrimation, and dryness of the eyes or mouth. None had orthostatic hypotension. Autonomic testing revealed mild-to-moderate abnormalities in all five affected subjects and minor abnormalities in the three oldest, asymptomatic, at-risk subjects. Findings in affected subjects consisted of preganglionic sudomotor dysfunction in all five, impaired cardiovagal function in three, and reduced or absent pupillary near responses in four. Tests of adrenergic function were normal in all subjects. The degree of autonomic dysfunction correlated significantly with disease duration and with indices of disease severity. In conclusion, there is evidence in PPND of a disturbance in the central autonomic network.

Adult↗
PubMed2002

The human sideroflexin 5 (SFXN5) gene: sequence, expression analysis and exclusion as a candidate for PARK3.

Parkinson's disease (PD) is a common neurodegenerative disorder with clinical features of bradykinesia, rigidity and resting tremor resulting from the deficiency of dopamine in the nigrostriatal system. Previously we mapped a susceptibility gene for an autosomal dominant form of PD to a 10.6 cM region of chromosome 2p (PARK3; OMIM 602404). Here we report the identification and characterization of the human sideroflexin 5 gene (SFXN5), which maps to the critical PARK3 region. Database analysis and 5'-RACE (rapid amplification of cDNA ends) identified a 4191 bp cDNA, encoding a predicted protein of 340 amino acids. The genomic sequence and structure of SFXN5 confirmed the cDNA sequence. Northern blot analysis revealed a single SFXN5 transcript of approximately 4.3 kb, which was primarily expressed in the brain. An examination of SFXN5 expression in specific regions of the human brain revealed high levels of expression in all regions analyzed. Sequence analysis of 2p13 linked individuals affected with PD did not reveal any potentially pathogenic mutations within SFXN5, suggesting SFXN5 does not correspond to PARK3.

Amino Acid Sequence↗