Browsing by Author "Carr, J."

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    Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: A case-control study
    (2011) Ross, O. A.; Soto-Ortolaza, A. I.; Heckman, M. G.; Aasly, J. O.; Abahuni, N.; Annesi, G.; Bacon, J. A.; Bardien, S.; Bozi, M.; Brice, A.; Brighina, L.; Van Broeckhoven, C.; Carr, J.; Chartier-Harlin, M. C.; Dardiotis, E.; Dickson, D. W.; Diehl, N. N.; Elbaz, A.; Ferrarese, C.; Ferraris, A.; Fiske, B.; Gibson, J. M.; Gibson, R.; Hadjigeorgiou, G. M.; Hattori, N.; Ioannidis, J. P. A.; Jasinska-Myga, B.; Jeon, B. S.; Kim, Y. J.; Klein, C.; Kruger, R.; Kyratzi, E.; Lesage, S.; Lin, C. H.; Lynch, T.; Maraganore, D. M.; Mellick, G. D.; Mutez, E.; Nilsson, C.; Opala, G.; Park, S. S.; Puschmann, A.; Quattrone, A.; Sharma, M.; Silburn, P. A.; Sohn, Y. H.; Stefanis, L.; Tadic, V.; Theuns, J.; Tomiyama, H.; Uitti, R. J.; Valente, E. M.; van de Loo, S.; Vassilatis, D. K.; Vilarino-Guell, C.; White, L. R.; Wirdefeldt, K.; Wszolek, Z. K.; Wu, R. M.; Farrer, M. J.
    Background: Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods: LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0·5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings: 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1·43, 95% CI 1·15-1·78; p=0·0012) and Asian individuals (A419V, 2·27, 1·35-3·83; p=0·0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0·82, 0·72-0·94; p=0·0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1·73, 1·20-2·49; p=0·0026), but no association was noted for R1628P (0·62, 0·36-1·07; p=0·087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4·48, 1·33-15·09; p=0·012).Interpretation: The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. Funding: Michael J Fox Foundation and National Institutes of Health. © 2011 Elsevier Ltd.
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    EMG/ENG services rendered by clinical neurophysiology technologists in solo practice
    (Health & Medical Publishing Group, 1998) Bill, P. L. A.; Fritz, V. U.; Eastman, R. W.; Gledhill, R. F.; Kruger, A. J.; Mafojane, N. A.; Saffer, S. D.; Carr, J.; Van Der Meyden, C. H.
    [No abstract available]
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    GCH1 in early-onset Parkinson's disease
    (2009) Cobb, S. A.; Wider, C.; Ross, O. A.; Mata, I. F.; Adler, C. H.; Rajput, A.; Rajput, A. H.; Wu, R. M.; Hauser, R.; Josephs, K. A.; Carr, J.; Gwinn, K.; Heckman, M. G.; Aasly, J. O.; Lynch, T.; Uitti, R. J.; Wszolek, Z. K.; Kapatos, G.; Farrer, M. J.
    Mutations in GTP-cyclohydrolase 1 (GCH1) cause autosomal dominant dopa-responsive dystonia (DRD), characterized by childhood-onset foot dystonia that later generalizes. DRD patients frequently present with associated Parkinsonism. Conversely, early-onset Parkinson's disease (EOPD) patients commonly display dystonia. Herein, we investigated the frequency of GCH1 mutations in a series of 53 familial EOPD patients (21 with dystonia) and screened them for mutations in PRKN, PINK1, and DJ-1. In addition, we examined a matched EOPD patient-control series for association of common variability at the GCH1 locus and EOPD susceptibility. No GCH1 coding change or copy-number abnormality was identified in familial EOPD patients. A novel 18-bp deletion was found in the proximal promoter (two patients, one control), which is expected to knock out two regulatory elements previously shown to regulate GCH1 transcription. No association was found between GCH1 variability and risk of EOPD. Fourteen (26.4%) familial EOPD patients had homozygous or compound heterozygous PRKN mutations. PRKN-positive patients were 10 years younger than PRKNnegative patients and had a twofold higher prevalence of dystonia. 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. © 2009 Movement Disorder Society.
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    Huntington's disease-like 2 in South Africa
    (Health and Medical Publishing Group (HMPG), 2008) Greenberg, Jacquie; Bardien, Soraya; Carr, J.
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    Neurologists and shoulder pain
    (Health & Medical Publishing Group, 2000) Butler, J.; Carr, J.
    [No abstract available]
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    South African guideline on deep brain stimulation for Parkinson’s disease
    (Health & Medical Publishing Group, 2017) Anderson, D. G.; Van Coller, R.; Carr, J.
    Background. Parkinson’s disease (PD) is a common neurodegenerative disease, associated with severe impairment of quality of life. Although the motor aspects of the illness are typically successfully treated with medications acting on the dopaminergic system, a number of patients encounter progressive difficulties associated with their medical treatment. Recommendations. Carefully selected patients will benefit from deep brain stimulation (DBS) treatment for their PD. Selection requires dopamine challenge testing and neuropsychological testing for the presence of cognitive impairment. Careful follow-up and programming of the DBS system are mandatory, and a major reason for DBS failure is inadequate programming and management of medication. Conclusion. DBS is a useful component of standard therapy for PD and may reduce symptoms, improve quality of life, promote patient independence and reduce healthcare costs by reducing requirements for medicine.