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1.
Jin-Whan Cho Sung-Yeon Kim Sung-Sup Park Beom S. Jeon 《JOURNAL OF CLINICAL NEUROLOGY》2009,5(1):29-32
Background and Purpose
The LRRK2 (PARK8; OMIM607060) substitution was recently identified as a causative mutation for Parkinson''s disease (PD). The pathologic heterogeneity of LRRK2-positive patients suggests that mutation of the LRRK2 gene is associated with the pathogenesis of PD and Parkinson-plus disorders, such as multiple system atrophy (MSA). We previously reported that the G2019S LRRK2 mutation-which is the most common LRRK2 mutation-was not found in a sample of 453 Korean PD patients. In the present study, we extended the screening for the G2019S mutation to a larger group of PD and MSA patients.Methods
We performed a genetic analysis of the G2019S mutation in 877 patients with PD and 199 patients with MSA using a standard PCR and restriction digestion method.Results
None of the subjects carried the G2019S mutation.Conclusions
The results of the present study support that the G2019S mutation is extremely rare in PD and is unlikely to be associated with MSA in the Korean population. 相似文献2.
Sofya N Pchelina Andrei F Yakimovskii Olga N Ivanova Anton K Emelianov Andrei H Zakharchuk Alexander L Schwarzman 《Movement disorders》2006,21(12):2234-2236
Among mutations associated with autosomal dominant and sporadic Parkinson's disease (PD) the G2019S substitution in the leucine-rich repeat kinase 2 (LRRK2) gene is the most frequently identified. To estimate its frequency in Russia, we analyzed 208 patients with PD from the Northwestern region of Russia. Of these, 51 patients were probands from families with PD compatible with autosomal dominant inheritance. The control group represented 161 subjects without neurological disorders settled in the same region. The frequency of the G2019S mutation was greater in familial PD (2 [3.9%] of 51) than in sporadic PD (1 [0.6%] of 157). In addition, this mutation was found in the proband's father, who also had PD, in 1 PD family, and in 1 carrier without signs of PD at age 40 in another PD family. All carriers were heterozygous for the G2019S mutation and reported the Ashkenazi Jewish origin. The mutation was not found in the control group. 相似文献
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Lack of G2019S LRRK2 mutation in a cohort of Taiwanese with sporadic Parkinson's disease. 总被引:3,自引:0,他引:3
Hon-Chung Fung Chiung-Mei Chen John Hardy Dena Hernandez Andrew Singleton Yih-Ru Wu 《Movement disorders》2006,21(6):880-881
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been shown to cause autosomal dominant and sporadic Parkinson's disease (PD). We report here the frequency of a common heterozygous mutation, 2877510G>A, which produces a glycine-to-serine amino acid substitution at codon 2019 in idiopathic Taiwanese PD. The extreme rarity of the G2019S mutation in our population suggests the occurrence of this mutation resulted from a common European founder. 相似文献
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Williams-Gray CH Goris A Foltynie T Brown J Maranian M Walton A Compston DA Sawcer SJ Barker RA 《Journal of neurology, neurosurgery, and psychiatry》2006,77(5):665-667
The LRRK2 G2019S mutation is the commonest genetic cause of Parkinson's disease (PD) identified to date, although estimates of its prevalence in idiopathic disease vary considerably. Our objectives were to determine G2019S mutation frequency in an unselected, community based cohort of idiopathic PD cases from the UK and to describe phenotypic characteristics among carriers. The mutation was present in two of 519 cases (0.4%) and none of 887 control individuals. The true prevalence of the mutation in idiopathic disease, its penetrance, and the phenotypic heterogeneity of associated cases have important implications for genetic screening in the clinical field. 相似文献
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《Movement disorders》2006,21(12):2257-2260
A total of 956 individuals with Parkinson's disease (PD) from 430 multiplex PD pedigrees were screened for 12 previously reported, pathogenic LRRK2 mutations: R793M, L1114L, I1371V, R1441C, R1441G, R1441H, Y1699C, M1869T, I2012T, I2020T, G2385R, and IVS31 +3G>A. Previous screening identified the LRRK2 G2019S mutation in 5% of our families. Only 1 of the 12 newly screened mutations, R1441C, was detected in a single family in our patient cohort. These results indicate that, although the G2019S mutation remains the most common mutation identified in familial PD patients, other mutations in LRRK2 are infrequent. © 2006 Movement Disorder Society 相似文献
7.
Frequency and phenotypes of LRRK2 G2019S mutation in Italian patients with Parkinson's disease. 总被引:2,自引:0,他引:2
Roberta Marongiu Daniele Ghezzi Tamara Ialongo Francesco Soleti Antonio Elia Stefania Cavone Alberto Albanese Maria Concetta Altavista Paolo Barone Livia Brusa Pietro Cortelli Lucia Petrozzi Cesa Scaglione Paolo Stanzione Michele Tinazzi Massimo Zeviani Bruno Dallapiccola Anna Rita Bentivoglio Enza Maria Valente Barbara Garavaglia 《Movement disorders》2006,21(8):1232-1235
To evaluate the frequency of the LRRK2 G2019S mutation in Italy, we tested 1,072 probands with Parkinson's disease (PD; 822 sporadic and 250 familial): 20 patients (1.9%) carried the G2019S mutation, 11 patients (1.3%) were sporadic, and 9 (4.3%) had a positive family history. Considering only probands with autosomal dominant inheritance, the G2019S frequency raises to 5.2%. All presented a typical phenotype with variable onset and shared the common ancestral haplotype. Mutation frequency raised from 1.2% in early onset PD to 4.0% in late onset PD. 相似文献
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Anat Mirelman PhD Talia Heman MsPT Kira Yasinovsky BS Avner Thaler MD Tanya Gurevich MD Karen Marder MD Susan Bressman MD Anat Bar‐Shira PhD Avi Orr‐Urtreger MD PhD Nir Giladi MD Jeffrey M. Hausdorff PhD 《Movement disorders》2013,28(12):1683-1690
Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine‐rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the motor phenotype. We quantitatively compared gait and mobility in patients with PD carriers of the G2019S mutation to non‐carrier patients with PD to better understand the genotype‐phenotype relationship. Fifty patients with PD carriers of the G2019S LRRK2 mutation and 50 age, disease duration, and disease severity matched PD non‐carriers were studied. An accelerometer quantified gait under three walking conditions: usual‐walking, dual‐tasking, and fast‐walking. The Unified Parkinson's Disease Rating Scale classified patients into PD sub‐types and the Timed Up and Go quantified mobility and fall risk. In all three walking conditions, gait variability was larger and the walking pattern was less consistent among the PD mutation carriers (P < 0.016). The PD carriers also took longer to complete the Timed Up and Go (P = 0.011) and were more likely to report having fallen in the previous year (P = 0.018). 64% of the PD carriers were classified as belonging to the postural‐instability‐gait‐difficulty (PIGD) sub‐type compared to only 17% of the PD non‐carriers (P < 0.0001). Among patients with PD, the G2019S mutation in the LRRK2 gene is apparently associated with increased gait variability, an increased fall risk, and the PIGD sub‐type. Therapeutic approach specifically designed to delay gait disturbances and falls may be justified in patients who carry the G2019S mutation. © 2013 International Parkinson and Movement Disorder Society 相似文献
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Hirotaka Iwaki MD Cornelis Blauwendraat PhD Mary B. Makarious BSc Sara Bandrés-Ciga PhD Hampton L. Leonard MS J. Raphael Gibbs PhD Dena G. Hernandez PhD Sonja W. Scholz MD Faraz Faghri MS International Parkinson's Disease Genomics Consortium Mike A. Nalls PhD Andrew B. Singleton PhD 《Movement disorders》2020,35(5):774-780
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Sharma S Bandopadhyay R Lashley T Renton AE Kingsbury AE Kumaran R Kallis C Vilariño-Güell C O'Sullivan SS Lees AJ Revesz T Wood NW Holton JL 《Neuropathology and applied neurobiology》2011,37(7):777-790
S. Sharma, R. Bandopadhyay, T. Lashley, A. E. M. Renton, A. E. Kingsbury, R. Kumaran, C. Kallis, C. Vilariño‐Güell, S. S. O'Sullivan, A. J. Lees, T. Revesz, N. W. Wood and J. L. Holton (2011) Neuropathology and Applied Neurobiology 37, 777–790 LRRK2 expression in idiopathic and G2019S positive Parkinson's disease subjects: a morphological and quantitative study Aims: Mutations in the gene encoding leucine‐rich repeat kinase‐2 (LRRK2) have been established as a common genetic cause of Parkinson's disease (PD). The distribution of LRRK2 mRNA and protein in the human brain has previously been described, although it has not been reported in PD cases with the common LRRK2 G2019S mutation. Methods: To further elucidate the role of LRRK2 in PD, we determined the localization of LRRK2 mRNA and protein in post‐mortem brain tissue from control, idiopathic PD (IPD) and G2019S positive PD cases. Results: Widespread neuronal expression of LRRK2 mRNA and protein was recorded and no difference was observed in the morphological localization of LRRK2 mRNA or protein between control, IPD and G2019S positive PD cases. Using quantitative real‐time polymerase chain reaction, we demonstrated that there is no regional variation in LRRK2 mRNA in normal human brain, but we have identified differential expression of LRRK2 mRNA with significant reductions recorded in limbic and neocortical regions of IPD cases compared with controls. Semi‐quantitative analysis of LRRK2 immunohistochemical staining demonstrated regional variation in staining intensity, with weak LRRK2 immunoreactivity consistently recorded in the striatum and substantia nigra. No clear differences were identified in LRRK2 immunoreactivity between control, IPD and G2019S positive PD cases. LRRK2 protein was identified in a small proportion of Lewy bodies. Conclusions: Our data suggest that widespread dysregulation of LRRK2 mRNA expression may contribute to the pathogenesis of IPD. 相似文献
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Differential Phospho-Signatures in Blood Cells Identify LRRK2 G2019S Carriers in Parkinson's Disease
Alicia Garrido MD Enrique Santamaría PhD Joaquín Fernández-Irigoyen PhD Marta Soto MSc Cristina Simonet MD Manel Fernández Donina Obiang RN Eduardo Tolosa MD PhD María-José Martí MD PhD Shalini Padmanabhan PhD Cristina Malagelada PhD Mario Ezquerra PhD Rubén Fernández-Santiago PhD 《Movement disorders》2022,37(5):1004-1015
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Javier Ruiz‐Martínez MD PhD Patricia de la Riva MD Maria C. Rodríguez‐Oroz MD PhD Elisabet Mondragón Rezola MD Alberto Bergareche MD Ana Gorostidi PhD Belen Gago PhD Ainara Estanga Nerea Larrañaga MD PhD Cristina Sarasqueta MD PhD Adolfo López de Munain MD PhD José F. Martí Massó MD PhD 《Movement disorders》2014,29(6):750-755
An inverse relationship between Parkinson's disease (PD) and cancer has been described. However, the association between cancers and genetic forms of PD, in particular the R1441G mutation in the LRRK2 gene, is not well known. The objective of this work was to analyze cancer prevalence in PD patients with R1441G or G2019S mutations in LRRK2, and in idiopathic PD (iPD). A total of 732 patients with PD (70 and 25 carriers of R1441G or G2019S mutations, respectively), and 177 controls, were linked using a population‐based cancer registry of the Spanish province of Gipuzkoa. Cancer prevalence was not significantly higher in PD‐G2019S carriers (20%) than in PD‐R1441G carriers (14.3%), iPD (13.8%), or controls (12.5%). With the exception of a high prevalence of hematological cancers (crude odds ratio of 7.1) in the R1441G group, specific cancer types were not increased in PD mutation carriers. In both the carrier and iPD groups, cancers were diagnosed after the onset of PD. PD patients had a similar prevalence of cancer to control subjects. There was no increased association between G2019S or R1441G mutations and any type of cancer. Although there was a higher prevalence of hematological cancers in the R1441G group, the low number of such cancers overall makes this finding of uncertain significance. There was a slightly higher but not statistically significant prevalence of non‐skin cancers in the G2019S group, suggesting that further study to evaluate the association should be undertaken prior to ascribing an increased cancer risk to this population. © 2013 International Parkinson and Movement Disorder Society 相似文献
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José‐Félix Martí‐Massó Javier Ruiz‐Martínez Maria J. Bolaño Irune Ruiz Ana Gorostidi Fermin Moreno Isidre Ferrer Adolfo López de Munain 《Movement disorders》2009,24(13):1998-2001
We report the neuropathological findings in a patient with Parkinson's disease (PD) associated with Basque R1441G‐LRRK2/dardarin mutation. The patient was a man with disease onset at 68 years of age, with unilateral rest tremor; the Parkinsonism was well controlled with medication for 15 years. He died at the age of 86, after 18 years of evolution. The neuropathological examination disclosed mild neuronal loss in the substantia nigra pars compacta without α‐synuclein, tau, LRRK2, or ubiquitin cytoplasmic inclusions. Lewy bodies and Lewy neurites were absent. This is the first neuropathological study of PD associated with brain with the R1441G mutation in LRRK2. © 2009 Movement Disorder Society 相似文献
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Sierra M González-Aramburu I Sánchez-Juan P Sánchez-Quintana C Polo JM Berciano J Combarros O Infante J 《Movement disorders》2011,26(13):2343-2346
The frequency and penetrance of the LRRK2 G2019S mutation varies considerably in different Parkinson disease (PD) populations. This information is essential both for clinical purposes and genetic counseling. The objective of this study was to estimate the prevalence and penetrance of the G2019S mutation of the LRRK2 gene in a small region in northern Spain (Cantabria). The G2019S mutation was tested in 367 consecutive patients with PD attended as outpatients in a tertiary Hospital in Northern Spain, and 126 at-risk family members of probands were also investigated for G2019S mutation and disease status. The gene penetrance was estimated in terms of cumulative age-specific incidence of PD by the Kaplan-Meier method. Thirty-two PD patients (8.7%) carried the G2019S mutation. Penetrance estimation of the G2019S mutation was 2% at 50 years, 12% at 60 years, 26% at 70 years, and 47% at 80 years. The frequency of the G2019S mutation of the LRRK2 gene in PD patients from Cantabria is among the highest reported so far after North African Arabs and Ashkenazi Jews. At the age of 80 years only one-half of G2019S mutation carriers manifest motor symptoms of PD. 相似文献
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Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non‐Ashkenazi Jewish ancestry 下载免费PDF全文
Annie J. Lee MS Yuanjia Wang PhD Roy N. Alcalay MD MSc Helen Mejia‐Santana MS Rachel Saunders‐Pullman MD MPH MS Susan Bressman MD Jean‐Christophe Corvol MD PhD Alexis Brice MD Suzanne Lesage PhD Graziella Mangone MD Eduardo Tolosa MD Claustre Pont‐Sunyer MD Dolores Vilas MD Birgitt Schüle MD Farah Kausar PhD Tatiana Foroud PhD Daniela Berg MD Kathrin Brockmann MD Stefano Goldwurm MD PhD Chiara Siri PsyD Rosanna Asselta PhD Javier Ruiz‐Martinez MD PhD Elisabet Mondragón MD Connie Marras MD PhD Taneera Ghate MSc Nir Giladi MD Anat Mirelman PhD Karen Marder MD MPH for the Michael J. Fox LRRK Cohort Consortium 《Movement disorders》2017,32(10):1432-1438
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Javier Ruiz‐Martínez MD Ana Gorostidi PhD Estibaliz Goyenechea PhD Ainhoa Alzualde PhD Juan José Poza MD PhD Francisco Rodríguez MD Alberto Bergareche MD Fermín Moreno MD Adolfo López de Munain MD PhD José F. Martí Massó MD PhD 《Movement disorders》2011,26(11):2026-2031
It has been proposed that olfactory tests and metaiodobenzylguanidine cardiac scintigraphy may help diagnose idiopathic Parkinson's disease in the premotor phase. However, it is not clear what value these tests have in all patients with Parkinson's disease and, particularly, in those who carry mutations in LRRK2. The objective was to analyze olfactory dysfunction and the changes in cardiac I‐metaiodobenzylguanidine uptake in patients with Parkinson's disease carrying the R1441G and G2019S mutations in LRRK2, and in patients with Parkinson's disease with no known mutations. Patients with Parkinson's disease were screened for R1441G and G2019S LRRK2 gene mutations and classified as LRRK2 mutation carriers or noncarriers. A total of 190 patients with Parkinson's disease (44 LRRK2 mutation carriers) were tested for olfactory dysfunction using the Brief Smell Identification Test. Cardiac 123I‐metaiodobenzylguanidine scintigraphy was performed on 90 patients with Parkinson's disease (27 LRRK2 mutation carriers). Thirty‐six percent of patients with LRRK2 mutations have hyposmia, compared to 75% of noncarrier patients with Parkinson's disease (P < .001). Sixty‐six percent of LRRK2 mutation carriers have low early metaiodobenzylguanidine uptake, compared to 86% of noncarriers (P = .048). Similarly, the heart/mediastinum ratio in delayed metaiodobenzylguanidine images appeared to differ between these groups of patients with Parkinson's disease, although these results did not reach statistical significance. The data obtained indicate that olfactory and cardiac impairment is less prevalent when Parkinson's disease is associated with mutations in LRRK2, although the underlying mechanisms for this difference remain unclear. Thus, such screening would be less useful to detect the premotor phase in asymptomatic relatives who carry mutations in LRRK2 than in cases not associated with LRRK2. © 2011 Movement Disorder Society 相似文献