Z K Wszolek

..There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments...

..To describe the brain MRI characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS) with known mutations in the colony-stimulating factor 1 receptor gene (CSF1R) on chromosome 5...

..4,617 controls) and PD (678 PDs vs. 712 controls) for association with disease risk (case-controls), age-at-diagnosis (cases) and brain gene expression levels (autopsied subjects)...

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..Care is therefore supportive. Occupational and physical therapy for gait dysfunction and speech therapy for dysarthria is essential. Prognosis is variable depending on the type of ADCA and even among kindreds...

..The aim of this study was to identify TOR1A Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia...

..The prognosis and rate of the disease's progression vary considerably among individual patients and genetic kindreds, ranging from life expectancies of several months to several years, and, in exceptional cases, as long as two decades...

..The definitive diagnosis of FTDP-17 requires a set of clinical and pathological features combined with a molecular genetic analysis. Currently, there is no known effective treatment for FTDP-17...

..Previous epidemiologic and genetic studies have suggested a link between Parkinson disease (PD), essential tremor (ET), and restless legs syndrome (RLS)...

..To report genealogic, clinical, imaging, neuropathologic, and genetic data from a Canadian kindred with dystonia and brain calcinosis originally described in 1985...

..Whilst an association between the tau gene (MAPT)-containing H1 haplotype and supranuclear gaze palsy (PSP) has long been recognized, the effect of H1 on risk for Parkinson's disease (PD) has remained more contentious...

..To use a case-control study to assess and compare patterns of gray matter loss across groups of subjects with different mutations in the microtubule-associated protein tau (MAPT) gene...

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..To use multiple serial MRI to assess rates and trajectories of brain and hippocampal atrophy in subjects with frontotemporal dementia (FTD) with progranulin (GRN) or microtubule-associated protein tau (MAPT) gene mutations...

..To determine the proton magnetic resonance spectroscopy ((1)H MRS) changes in carriers of microtubule-associated protein (MAPT) mutations in a case-control study...

..Genetic studies suggested linkage to the PARK8 locus on chromosome 12...

..Recently, an association was reported between the calcium buffer, calbindin (rs1805874) and risk of PD in a Japanese patient-control series...

..The Lrrk2 protein is a member of the ROCO family, which also includes Lrrk1 and Dapk1. Functional genetic variants of the DAPK1 gene (rs4877365 and rs4878104) have been previously associated with Alzheimer's disease...

..In the current study, we attempt to validate previously published findings, evaluating gene-gene interactions between SNCA, MAPT, and GSK3B in association with PD...

..5 Mb. Analysis of 14 genes within the region did not reveal any potentially pathogenic mutations segregating with the disease, implying that none of these genes are likely candidates for PARK3...

..To compare patterns of gray matter loss in subjects with mutations in the progranulin (PGRN) gene to subjects with mutations in the microtubule-associated protein tau (MAPT) gene...

..This study reports clinical, genetic and neuropathologic investigations of Perry syndrome...

..rs5848 is located within a micro-RNA binding site and affects the expression of GRN...

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..However, gender may be an important factor related to the expression of PD features during the symptomatic disease course...

..This study does not support a significant role for genetic variation at the GCH1 locus in EOPD. However, our results further highlight the relevance of PRKN screening in familial EOPD...

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..Despite recent advances in the understanding of the tauopathies, there are still no curative therapies available. It is hoped that studies in transgenic tau animal models will lead to the development of successful treatments...

..CONCLUSION: Thalamic DBS is generally a well-tolerated and effective treatment for ET. Methodological and analytical recommendations are provided for the evaluation of long-term outcome...

..Several dominantly inherited pathogenic substitutions have been identified in different domains of the Lrrk2 protein. Herein, we characterize the clinical and genetic features associated with Lrrk2 p.R1441C...

..Phenotypic similarity among familial and sporadic PD indicates that a similar topographic distribution of the nigrostriatal lesion exists in patients with either form of PD regardless of apparent genetic influence...

..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...

..15, P=0.27). When combining all four series the observed trend was statistically significant (OR: 1.30, P<0.001). This study shows that reappraisal of publicly available results of GWAS may help nominate new risk factors for PD...

..Our work highlights the fact that a proportion of clinically typical, late-onset PD cases have a genetic basis...

..CONCLUSIONS: Unilateral thalamic stimulation significantly improves midline tremor, and subsequent bilateral thalamic stimulation offers an additional incremental improvement in midline tremor control...

..05). CONCLUSION: Essential tremor is a slow, progressive disease. The rate of disease progression and the factors associated with disease progression may vary throughout the disease course...

..Thus, the tau haplotype carrying the mutation and the tau genotype may be related to the clinical phenotype throughout the disease course...

..Subsequent screening efforts in familial, mainly early-onset, primary dystonia identified additional THAP1 sequence variants in non-Amish subjects...

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..This supports HDLS and POLD being referred collectively as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)...

..PRKN, PINK1 and DJ1 mutations cause early-onset recessively inherited PD. Autosomal dominant dementia and parkinsonism is caused by mutations in the MAPT gene, and in the most recently discovered PGRN gene...

..Patients carrying an LRRK2 mutation display significant variability of clinical and pathologic phenotypes across and within affected families...

..This study further expands the clinical and pathological spectrum of PGRN mutations, and suggests the diagnosis could be missed in some individuals with atypical presentations...

..To determine the proportion of individuals in a clinic-based setting that present with asymmetric Parkinson disease (PD) and identify predictive factors associated with asymmetric symptoms...

..In addition, results suggest that letter fluency may be a sensitive predictor of incipient PPND...

..Thus, the clinical and pathological findings in this family with autosomal dominant parkinsonism are similar to those of sporadic Parkinson's disease...

..A founder effect indicated by a shared disease haplotype was seen only in two Japanese families. The N279K mutation can develop independently in different parts of the world...

..To report a new American family with hereditary diffuse leukoencephalopathy with spheroids (HDLS), including serial, presymptomatic and symptomatic, cranial MRIs from the proband...

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..Further studies will examine reasons for the vulnerability of selected neuronal populations in Perry syndrome, and the link between the genetic defect and TDP-43 pathology...

..It is hoped that future studies of these families will also lead to finding the curative treatments for the tauopathies...

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..In general, the disease phenotype was similar between men and women, suggesting that sex may have little or no influence on the development, expression, or progression of the PSP phenotype...

..This study evaluated whether genetic risk factors for CAD and MI also affect susceptibility to ischaemic stroke in Caucasians and African Americans...

..However we can not rule out other genetic variation at the LRRK2 locus may play a role in parkinsonian disorders with amyotrophic lateral sclerosis and may be considered candidates for genetic screening...

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..e. burning and tingling with stimulation). CONCLUSION: DBS is associated with stable tremor control in PD. Side-effects are typically easily managed with stimulation adjustments, although in some cases lead replacement may be required...

..The authors found evidence against linkage to IBGC1 in five of the six families supporting previous preliminary studies demonstrating genetic heterogeneity in familial IBGC...

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..Our findings show that DCTN1 mutations, previously associated with motor neuron disease, can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders...

..We found no evidence of association between FGF20 variability and PD risk, and no relationship between the rs12720208 genotype, FGF20 and alpha-synuclein protein levels...

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..Our data indicate that genetic variability in USP24 is associated with PD. Although our work extends and confirms a previous report, the observed effect size does not explain the PARK10 linkage peak...

..Taken together our results do not support a role for Omi/HtrA2 variants in the pathogenesis of Parkinson's disease...

..Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders...

..16, n=2696). We observed a modest association between DBH -1021C>T and AAO in the combined series (p=0.01). Taken together, these findings indicate that DBH -1021C>T does not play a major role in the pathogenesis of Parkinson's disease...

..These results suggest that alterations in nutrient intake or metabolism could reflect early changes in the central autonomic network preceding the emergence of classical extrapyramidal manifestations of PD...

..Statistical analysis failed to identify significant differences in the frequency of these variants between the case and control groups; therefore our results do not support a role for these DRD3 and HS1BP3 variants in PD...

..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...

..Electrophysiology yielded remarkable findings in those asymptomatic at-risk individuals that carried the N279K tau mutation...

..Given the ethnic-specific LRRK2 variation previously identified in PD further studies in under-represented populations are warranted...

..In addition, clinical treatment of PD remains largely unaltered by the results of genetic testing...

..Undoubtedly further research into the FTDP-17 will contribute to the development of a successful treatment for these devastating degenerative diseases of the c.n.s...

..Our study demonstrates a significant association between LINGO1 rs9652490 and essential tremor (P = 0.014) and Parkinson disease (P = 0.0003), thus providing the first evidence of a genetic link between both diseases...

..We conclude that in certain circumstances genetic studies may provide definitive arbitration of validity of clinical and pathological diagnostic criteria...

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..There are no reports on the possible association of rapid eye movement sleep without atonia and RBD with any familial tauopathy...

..Examine the characteristics of an essential tremor (ET) clinical cohort including base-rate variability of several commonly accepted diagnostic criteria...

..Our data suggest that the association between ELAVL4 and PD previously observed might be explained by a Celtic-founder effect...

..These results support the assertion that the H1/H1 genotype may contribute to the earlier occurrence of clinical symptoms...

..These data do not support a role for this common variant in PD etiology...

..Neuropathology shows severe neuronal loss in the substantia nigra, less prominent neuronal loss in the locus coeruleus, and no or few Lewy bodies. In this review, we also propose diagnostic criteria for this condition...

..Comparison of evolutionary interspecies sequences of LRRK1 and LRRK2 suggests they diverged from a common founder gene...

..Other, newer agents are not subject to this interaction, and further studies are needed to define their role in the management of seizures in transplant patients...

..A role for Lrrk2 in neurogenesis might provide further insight into the aberrant role of mutant protein in age-associated neurodegeneration with pleomorphic pathology...

..To report the study of a multigenerational Swiss family with dopa-responsive dystonia (DRD)...

..9). Patients with PD who newly developed gambling behavior were more likely to have been taking Pramipexole than other anti-PD medication. However, the association between Pramipexole and gambling behavior is not necessarily etiologic...

..To examine predictive factors associated with onset of depression among individuals diagnosed with Parkinson's disease (PD)...

..Five patients (1.2%) carry intermediate-size alleles (41-54 CGG repeats). Expansions within the FMR1 gene are not associated with PD in our study...

..Results of genealogical and molecular genetic studies determined that the families were not related. The N279K mutations found in both families have independent origins...

..Since DNA damage and lysosomal dysfunction have been implicated in aging and neurodegenerative processes, both genes are viable candidates for conferring risk of disease...

..S402_P411delinsGGGG) which is predicted to expand a conserved poly-glycine motif. Our findings extend the mutation spectrum in FUS leading to ALS and describe the first de novo mutation in FUS...

..To determine the association of the genes that encode alpha-, beta-, and gamma-synuclein (SNCA, SNCB, and SNCG, respectively) with diffuse Lewy body disease (DLBD)...

..The clinical and neuropathologic features of frontotemporal dementia with parkinsonism linked to chromosome 17 and the nature of the mutations in the progranulin and microtubule-associated protein tau genes are emphasized...

..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...

..Seven of these coding changes seem to be pathogenic, as they segregate with disease and were not identified within controls. No multiplications or deletions were identified...

..To enhance the sensitivity and specificity of the clinical diagnosis of progressive supranuclear palsy (PSP), neuroradiological parameters established in pathologically proven cases are needed...