Search results for " AMYOTROPHIC LATERAL SCLEROSIS"
showing 10 items of 27 documents
Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis.
2013
MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration. © 2014 Nature America, Inc. All rights reserved.
CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients
2015
Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) comorbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n= 64) and apparently sporadic ALS (n= 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in 2 unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHC…
HFE p.H63D polymorphism does not influence ALS phenotype and survival.
2015
It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significa…
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
2018
© 2018 Elsevier Inc.
ATXN2 trinucleotide repeat length correlates with risk of ALS
2017
We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carry…
Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomized, double blind, placebo controlled, phase III study.
2015
Objective To assess the efficacy of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). Methods Patients with probable laboratory-supported, probable or definite ALS were enrolled by 25 Italian centres and randomly assigned (1:1) to receive intravenous rhEPO 40 000 IU or placebo fortnightly as add-on treatment to riluzole 100 mg daily for 12 months. The primary composite outcome was survival, tracheotomy or >23 h non-invasive ventilation (NIV). Secondary outcomes were ALSFRS-R, slow vital capacity (sVC) and quality of life (ALSAQ-40) decline. Tolerability was evaluated analysing adverse events (AEs) causing withdrawal. The randomisation sequence was computer-…
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…
The importance of the reproducibility of oropharyngeal swallowing in amyotrophic lateral sclerosis. An electrophysiological study
2017
Abstract Objective To investigate electrophysiologically the reproducibility of oropharyngeal swallowing in patients with ALS. Methods We enrolled 26 ALS patients, both with and without clinical signs of dysphagia, and 30 age-matched controls. The reproducibility of the electrophysiological signals related to the oral phase (electromyographic activity of the submental/suprahyoid muscles) and the pharyngeal phase (laryngeal-pharyngeal mechanogram) of swallowing across repeated swallows was assessed. To do this we computed two similarity indexes (SI) by using previously described mathematical algorithms. Results The reproducibility of oropharyngeal swallowing was significantly reduced both in…
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…
Generalised sensory system abnormalities in amyotrophic lateral sclerosis: a European multicentre study.
2007
International audience; BACKGROUND: Amyotrophic lateral sclerosis (ALS) is defined as a disease of the motor neurones, although several studies indicate involvement of the sensory nervous system. AIM: To evaluate the sensory nerve conduction studies (NCS) in 88 patients with ALS as part of a European multicentre study. METHODS: Seven European clinical neurophysiologists examined consecutive series of ALS patients. The examinations were peer reviewed, and the diagnosis of ALS was confirmed clinically. RESULTS: 20 (22.7%) patients with ALS had sensory NCS abnormalities in at least one nerve. Of those, 11 (12.5% of all patients) obtained an additional peer review diagnosis of electrophysiologi…