Search results for "C9ORF72"

showing 10 items of 17 documents

Cognitive correlates in amyotrophic lateral sclerosis: a population-based study in Italy.

2014

Background There is less data available regarding the characteristics of cognitive impairment in patients with amyotrophic lateral sclerosis (ALS) in a population-based series. Methodology Patients with ALS incident in Piemonte, Italy, between 2009 and 2011 underwent an extensive neuropsychological battery. Cognitive status was classified as follows: normal cognition, frontotemporal dementia (ALS-FTD), executive cognitive impairment (ALS-ECI), non-executive cognitive impairment (ALS-NECI), behavioural impairment (ALS-Bi), non-classifiable cognitive impairment. We also assessed 127 age-matched and gender-matched controls identified through patients’ general practitioners. Results Out of the …

Malemedicine.medical_specialtyPediatricsNeuromuscular diseasePopulationNeuropsychological TestsSuperoxide Dismutase-1Risk FactorsmedicineDementiaHumansEPIDEMIOLOGYAmyotrophic lateral sclerosisPsychiatryeducationCognitive reserveAgededucation.field_of_studyC9orf72 ProteinSuperoxide DismutaseDEMENTIAAmyotrophic Lateral SclerosisProteinsCognitionmedicine.diseaseSurvival AnalysisALS DEMENTIA EPIDEMIOLOGYDNA-Binding ProteinsPsychiatry and Mental healthItalyCase-Control StudiesMutationSurgeryFemaleSettore MED/26 - NeurologiaNeurology (clinical)ALSPsychologyCognition DisordersMotor neurone diseaseFrontotemporal dementia
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Clinical characteristics of patients with familial amyotrophic lateral sclerosis carrying the pathogenic GGGGCC hexanucleotide repeat expansion of C9…

2012

A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72, a gene located on chromosome 9p21, has been recently reported to be responsible for 40% of familial amyotrophic lateral sclerosis cases of European ancestry. The aim of the current article was to describe the phenotype of amyotrophic lateral sclerosis cases carrying the expansion by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotrophic lateral sclerosis. We collected DNA and analysed phenotype data for 141 index Italian familial amyotrophic l…

MaleParentsPathologyphenotype-genotype correlationCohort Studies0302 clinical medicineC9orf72amyotrophic lateral sclerosigeneticsAmyotrophic lateral sclerosisAge of Onsetamyotrophic lateral sclerosis; familial als; C9Orf72; phenotype-genotype correlation0303 health sciencesSex CharacteristicsDNA Repeat ExpansionAdult Age of Onset Aged Amyotrophic Lateral Sclerosis; genetics/pathology Cohort Studies DNA Repeat Expansion DNA; genetics Female Humans Italy Male Middle Aged Mutation; genetics Parents Pedigree Phenotype Proteins; genetics Sex Characteristics Survival AnalysisMiddle Aged3. Good healthPedigreeSettore MED/26 - NEUROLOGIAPhenotypeItalyC9Orf72Settore MED/26 - NeurologiaFemaleFrontotemporal dementiaAdultmedicine.medical_specialtySOD1BiologyTARDBP03 medical and health sciencesInternal medicinemedicineHumans030304 developmental biologyAgedamyotrophic lateral sclerosis familial ALS C9ORF72 gene phenotype–genotype correlationC9orf72 ProteinAmyotrophic Lateral Sclerosisgenetics/pathologyProteinsOriginal ArticlesDNAmedicine.diseaseSurvival AnalysisC9orf72 ProteinSettore BIO/18 - Geneticaamyotrophic lateral sclerosis; familial ALS C9ORF72 gene; phenotype-genotype correlation;MutationNeurology (clinical)Age of onsetTrinucleotide repeat expansionfamilial al030217 neurology & neurosurgery
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Clinical profile of motor neuron disease patients with lower urinary tract symptoms and neurogenic bladder

2017

Introduction: Lower urinary tract symptoms (LUTS) are frequent in motor neuron disease (MND) patients, but clinical factors related to them are unknown. We describe differences in LUTS among MND phenotypes and their relationship with other clinical characteristics, including prognosis. Methods: For this study, we collected clinical data of a previously published cohort of patients diagnosed with classical amyotrophic lateral sclerosis (cALS), progressive muscular atrophy (PMA) or primary lateral sclerosis (PLS) with and without LUTS. Familial history was recorded and the C9ORF72 expansion was analysed in the entire cohort Patients were followed-up for survival until August 2016. Results: Fi…

Malemedicine.medical_specialtyNeurogenic bladder030232 urology & nephrologyDiseaseMuscular Atrophy Spinal03 medical and health sciencesSex Factors0302 clinical medicineLower Urinary Tract SymptomsLower urinary tract symptomsC9orf72Primary lateral sclerosisInternal medicinemedicineHumansLower urinary tract symptomsMotor neuron diseaseMotor Neuron DiseaseUrinary Bladder NeurogenicFamily historyAmyotrophic lateral sclerosisAgedPrimary Lateral SclerosisC9orf72 Proteinbusiness.industryAmyotrophic Lateral SclerosisMiddle AgedProgressive muscular atrophyPrognosismedicine.diseaseAmyotrophic lateral sclerosisSurvival AnalysisSurgeryUrodynamicsCross-Sectional StudiesPhenotypeNeurologyProgressive muscular atrophyAmyotrophic lateral sclerosis Lower urinary tract symptoms Motor neuron disease Neurogenic bladder Primary lateral sclerosis Progressive muscular atrophy UrodynamicsMultivariate AnalysisCohortFemaleNeurology (clinical)business030217 neurology & neurosurgeryFollow-Up Studies
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ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion

2015

Abstract There are indications that both familial amyotrophic lateral sclerosis (ALS) and sporadic ALS phenotype and prognosis are partly regulated by genetic and environmental factors, supporting the theory that ALS is a multifactorial disease. The aim of this article was to assess the role of ATXN2 intermediate length repeats in a large series of Italian and Sardinian ALS patients and controls carrying a pathogenetic C9ORF72 GGGGCC hexanucleotide repeat. A total of 1972 ALS cases were identified through the database of the Italian ALS Genetic consortium, a collaborative effort including 18 ALS centers throughout Italy. The study population included: (1) 276 Italian and 57 Sardinian ALS ca…

Male0301 basic medicineAgingC9ORF72Genetic Association Studie030105 genetics & heredityBiologySettore MED/03 - GENETICA MEDICA03 medical and health sciences0302 clinical medicineC9orf72medicineAlleleAmyotrophic lateral sclerosisAmyotrophic lateral sclerosiAgedAtaxin-2Regulator geneAmyotrophic lateral sclerosis; ATXN2; C9ORF72; Phenotype; Neuroscience (all); Medicine (all); Aging; Developmental Biology; Geriatrics and Gerontology; Neurology (clinical)GeneticsDNA Repeat ExpansionNeuroscience (all)ProteinMedicine (all)General NeuroscienceATXN2Middle AgedDNA Repeat Expansionmedicine.diseaseAmyotrophic lateral sclerosis3. Good healthC9orf72 ProteinAmyotrophic lateral sclerosis; ATXN2; C9ORF72; Phenotype; Neurology (clinical); Neuroscience (all); Aging; Developmental Biology; Geriatrics and GerontologyPhenotypeItalyPopulation studyFemaleSettore MED/26 - NeurologiaNeurology (clinical)Geriatrics and GerontologyTrinucleotide repeat expansion030217 neurology & neurosurgeryHumanDevelopmental Biology
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Characterization of the repeat expansion size in C9orf72 in amyotrophic lateral sclerosis and frontotemporal dementia

2013

Hexanucleotide repeat expansions within the C9orf72 gene are the most important genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The difficulty of developing a precise method to determine the expansion size has hampered the study of possible correlations between the hexanucleotide repeat number and clinical phenotype. Here we characterize, through a new non-radioactive Southern blot protocol, the expansion size range in a series of 38 ALS and 22 FTD heterozygous carriers of >30 copies of the repeat. Maximum, median and modal hexanucleotide repeat number were higher in ALS patients than in FTD patients (P < 0.05 in all comparisons). A higher median numb…

MaleHeterozygoteBiologyC9orf72GeneticsmedicineHumansAmyotrophic lateral sclerosisMolecular BiologyGenetics (clinical)GeneticsDNA Repeat ExpansionC9orf72 ProteinAmyotrophic Lateral SclerosisProteinsHeterozygote advantageTwins MonozygoticGeneral MedicineMiddle AgedDNA Repeat Expansionmedicine.diseaseC9orf72 ProteinBlotting SouthernFrontotemporal DementiaMutationFemaleAge of onsetTrinucleotide repeat expansionFrontotemporal dementia
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Dysfunction of attention switching networks in amyotrophic lateral sclerosis

2019

Objective To localise and characterise changes in cognitive networks in Amyotrophic Lateral Sclerosis (ALS) using source analysis of mismatch negativity (MMN) waveforms. Rationale The MMN waveform has an increased average delay in ALS. MMN has been attributed to change detection and involuntary attention switching. This therefore indicates pathological impairment of the neural network components which generate these functions. Source localisation can mitigate the poor spatial resolution of sensor-level EEG analysis by associating the sensor-level signals to the contributing brain sources. The functional activity in each generating source can therefore be individually measured and investigat…

MaleMismatch negativitySource localisationEEG ElectroencephalographyMismatch negativityNetworkElectroencephalographylcsh:RC346-429PET Positron emission tomographyCognition0302 clinical medicineC9orf72AttentionEEGAUROC Area under receiver operating characteristic curveAmyotrophic lateral sclerosisAged 80 and overmedicine.diagnostic_test05 social sciencesCognitive flexibilityBrainRegular ArticleElectroencephalographyCognitionMiddle AgedSTG Superior temporal gyrusNeurologyMTG Mid temporal gyrusDLPFC Dorsolateral prefrontal cortexlcsh:R858-859.7FemaleLCMV Linearly constrained minimum varianceIFG Inferior frontal gyrusAdultCognitive Neurosciencelcsh:Computer applications to medicine. Medical informatics050105 experimental psychologyCWIT Colour-word interference test03 medical and health sciencesfMRI Functional magnetic resonance imagingMEG MagnetoencephalographymedicineMMN Mismatch negativityHumans0501 psychology and cognitive sciencesRadiology Nuclear Medicine and imagingLS Amyotrophic Lateral SclerosisAAL Automated Anatomical Labellinglcsh:Neurology. Diseases of the nervous systemAEP Auditory evoked potentialAgedbusiness.industryAmyotrophic Lateral SclerosisIQR Interquartile rangeNeurophysiologyqEEG Quantitative EEGmedicine.diseaseNeurology (clinical)Nerve NetFunctional magnetic resonance imagingbusinessNeuroscience030217 neurology & neurosurgeryeLORETA Exact low-resolution brain electromagnetic tomographyNeuroImage: Clinical
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ALS-Related Mutant FUS Protein Is Mislocalized to Cytoplasm and Is Recruited into Stress Granules of Fibroblasts from Asymptomatic &lt;b&gt;&lt;i&gt;…

2017

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Amyotrophic lateral sclerosis (ALS) shows a strong genetic basis, with &lt;i&gt;SOD1&lt;/i&gt;, &lt;i&gt;FUS&lt;/i&gt;, &lt;i&gt;TARDBP&lt;/i&gt;, and &lt;i&gt;C9ORF72 &lt;/i&gt;being the genes most frequently involved&lt;i&gt;. &lt;/i&gt;This has allowed identification of asymptomatic mutation carriers, which may be of help in understanding the molecular changes preceding disease onset. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; We studied the cellular expression of FUS protein and the effect of heat-shock- and dithiothreitol-induced stress in fibroblasts from &lt;i&gt;FUS&lt;/i&gt; P525L mutation carriers, healthy controls, and pati…

0301 basic medicineBiologymedicine.diseaseSubcellular localizationTARDBPMolecular biology03 medical and health sciencesCell nucleus030104 developmental biology0302 clinical medicineStress granulemedicine.anatomical_structureNeurologyC9orf72CytoplasmmedicineNeurology (clinical)Amyotrophic lateral sclerosis030217 neurology & neurosurgeryRNA-Binding Protein FUSNeurodegenerative Diseases
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Estimation of the prevalence and incidence of motor neuron diseases in two Spanish regions: Catalonia and Valencia

2021

AbstractAccording to the degree of upper and lower motor neuron degeneration, motor neuron diseases (MND) can be categorized into amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS) or progressive muscular atrophy (PMA). Although several studies have addressed the prevalence and incidence of ALS, there is a high heterogeneity in their results. Besides this, neither concept has been previously studied in PLS or PMA. Thus, the objective of this study was to estimate the prevalence and incidence of MND, (distinguishing ALS, PLS and PMA), in the Spanish regions of Catalonia and Valencia in the period 2011–2019. Two population-based Spanish cohorts were used, one from Catalonia …

MaleMalalties neuromuscularsGene ExpressionSuperoxide Dismutase-10302 clinical medicinePrevalence030212 general & internal medicineAmyotrophic lateral sclerosisEstimation theoryPrimary Lateral Sclerosismedia_commonMotor neuronsMotor Neuronseducation.field_of_studyMultidisciplinaryIncidenceIncidence (epidemiology)QRMiddle AgedProgressive muscular atrophyNeuromuscular diseasesmedicine.anatomical_structureNeurones motoresNeurologyMedicineFemaleRiskSciencemedia_common.quotation_subjectPopulationBiologyArticleMuscular Atrophy Spinal03 medical and health sciencesmedicineHumansMotor Neuron DiseaseEspanyaEstimació Teoria de l'educationAgedEstimationSelection biasMotor neurons -- DiseasesModels StatisticalC9orf72 ProteinAmyotrophic Lateral SclerosisMotor neuronmedicine.diseaseRisk factorsSpainNeurones motores -- MalaltiesMutationBiomarkers030217 neurology & neurosurgeryDemography
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Genetic investigation of amyotrophic lateral sclerosis patients in south Italy: a two-decade analysis

2020

Amyotrophic lateral sclerosis (ALS) is a multifactorial disease characterized by the interplay of genetic and environmental factors. In the majority of cases, ALS is sporadic, whereas familial forms occur in less than 10% of patients. Herein, we present the results of molecular analyses performed in a large cohort of Italian ALS patients, focusing on novel and already described variations in ALS-linked genes. Our analysis revealed that more than 10% of tested patients carried a mutation in one of the major ALS genes, with C9orf72 hexanucleotide expansion being the most common mutation. In addition, our study confirmed a significant association between ALS patients carrying the ATNX-1 interm…

Male0301 basic medicineSanger sequencingAgingTime FactorsDiseaseCohort Studies03 medical and health sciencessymbols.namesake0302 clinical medicineRisk FactorsC9orf72HumansMedicineAmyotrophic lateral sclerosisRisk factorGenePathologicalAtaxin-1Genetic Association StudiesAmyotrophic lateral sclerosiSanger sequencingGeneticsDNA Repeat ExpansionC9orf72 ProteinMolecular analysibusiness.industryMolecular analysisGeneral NeuroscienceGenetic VariationAmyotrophic lateral sclerosismedicine.disease030104 developmental biologyItalyMutation (genetic algorithm)symbolsFemaleNeurology (clinical)Geriatrics and Gerontologybusiness030217 neurology & neurosurgeryDevelopmental BiologyNeurobiology of Aging
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Genomic portrait of a sporadic amyotrophic lateral sclerosis case in a large spinocerebellar ataxia type 1 family

2020

Background: Repeat expansions in the spinocerebellar ataxia type 1 (SCA1) gene ATXN1 increases the risk for amyotrophic lateral sclerosis (ALS), supporting a relationship between these disorders. We recently reported the co-existence, in a large SCA1 family, of a clinically definite ALS individual bearing an intermediate ATXN1 expansion and SCA1 patients with a full expansion, some of which manifested signs of lower motor neuron involvement. Methods: In this study, we employed a systems biology approach that integrated multiple genomic analyses of the ALS patient and some SCA1 family members. Results: Our analysis identified common and distinctive candidate genes/variants and related biolog…

Candidate geneSpinocerebellar Ataxia Type 1Medicine (miscellaneous)lcsh:MedicineNetworkBiologyArticle03 medical and health sciences0302 clinical medicinemulti-omics; networkC9orf72medicineCustomized aCGHAmyotrophic lateral sclerosisGene030304 developmental biologyTAF15Genetics0303 health sciencesMulti-omicslcsh:Rmedicine.diseaseAmyotrophic lateral sclerosisPhenotypeSCA1-MNNGSSpinocerebellar ataxiaSpinocerebellar ataxia030217 neurology & neurosurgeryPathway
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