Role of MAPT in Pure Motor Neuron Disease: Report of a Recurrent Mutation in Italian Patients.

Role of MAPT in Pure Motor Neuron Disease: Report of a Recurrent Mutation in Italian Patients. Neurodegener Dis. 2019 Mar 20;18(5-6):310-314 Authors: Origone P, Geroldi A, Lamp M, Sanguineri F, Caponnetto C, Cabona C, Gotta F, Trevisan L, Bellone E, Manganelli F, Devigili G, Mandich P Abstract The aim of our study was to evaluate the role of mutations in the MAPT gene in patients with pure amyotrophic lateral sclerosis (ALS). A cohort of 120 ALS patients, both sporadic and familial, without cognitive impairment was analyzed by next-generation sequencing with a multiple-gene panel comprising 23 genes, including MAPT, known to be associated with ALS and frontotemporal dementia. The presence of the C9orf72 expansion was also investigated. Twelve patients had mutations in the SOD1, TARDBP, MATR3, and FUS genes, while 10 patients carried the C9orf72 expansion. One female patient was found to carry the D348G mutation in MAPT, previously reported in an Italian family with lower motor neuron disease. Our patient presented both upper and lower motor neuron signs, early development of dyspnea, resting and kinetic tremor, and a slow disease course (> 11 years). The present case further broadens the clinical phenotype associated with MAPT mutations and suggests that, although rarely, MAPT mutations can cause ALS and, therefore, should be analyzed in ALS patients, especially in those with early breathing difficulties and long-lasting disease. PMID: 30893702 [...
Source: Neuro-Degenerative Diseases - Category: Neurology Authors: Tags: Neurodegener Dis Source Type: research

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Authors: Corcia P, Lumbroso S, Cazeneuve C, Mouzat K, Camu W, Vourc'h P, on Behalf the FILSLAN network Abstract Pathophysiology of amyotrophic lateral sclerosis (ALS) remains partially understood even though it is accepted worldwide that motor neuron death results from a pluri-factorial process with a variable role of genetic factors. Although not distinguishable from a clinical point of view, familial forms of ALS (fALS, 10% of cases) and sporadic forms (sALS, 90% of cases) can be described. Since the identification of superoxide dismutase 1 gene (SOD1) mutations, more than 30 genes have been linked to fALS. Among...
Source: Revue Neurologique - Category: Neurology Tags: Rev Neurol (Paris) Source Type: research
;dérique R Abstract Amyotrophic lateral sclerosis and frontotemporal dementia are two neurodegenerative diseases with currently no cure. These two diseases share a clinical continuum with overlapping genetic causes. Mutations in the CHMP2B gene are found in patients with ALS, FTD and ALS-FTD. To highlight deregulated mechanisms occurring in ALS-FTD linked to the CHMP2B gene, we performed a whole transcriptomic study on lumbar spinal cord from CHMP2Bintron5 mice, a model that develops progressive motor alterations associated with dementia symptoms reminiscent of both ALS and FTD. To gain insight into the tra...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
Publication date: 2019Source: International Review of Neurobiology, Volume 149Author(s): James B. RoweAbstractFrontotemporal dementia is a clinically and pathologically heterogeneous group of neurodegenerative disorders, with progressive impairment of behavior and language. They can be closely related to amyotrophic lateral sclerosis, clinically and through shared genetics and similar pathology. Approximately 40% of people with frontotemporal dementia report a family history of dementia, motor neuron disease or parkinsonism, and half of these familial cases are attributed to mutations in three genes (C9orf72, MAPT and PGRN...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
Publication date: Available online 21 November 2019Source: International Review of NeurobiologyAuthor(s): James B. RoweAbstractFrontotemporal dementia is a clinically and pathologically heterogeneous group of neurodegenerative disorders, with progressive impairment of behavior and language. They can be closely related to amyotrophic lateral sclerosis, clinically and through shared genetics and similar pathology. Approximately 40% of people with frontotemporal dementia report a family history of dementia, motor neuron disease or parkinsonism, and half of these familial cases are attributed to mutations in three genes (C9orf...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
The primary role of magnetic resonance imaging (MRI) in routine diagnostic work-up of motor neuron disease patients is currently still largely limited to exclusion of relevant non-degenerative pathologies. We here present an illustrative case of a 63-year-old woman with early stage Frontotemporal-Dementia-Amyotrophic-Lateral-Sclerosis (FTD-ALS) spectrum disorder showing a striking hypointense signal of the cortical band along the precentral gyrus, termed “Motor Band Sign” (MBS). Based on this finding, we analysed the frequency of the MBS in clinical routine MRIs in a large consecutive series of ALS patients (MR...
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Source Type: research
Purpose of review The fatal motoneuron disease amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a high contribution of genetic factors to pathogenesis, in probably both familial and sporadic ALS cases. State-of-the art sequencing techniques continue to reveal novel monogenic causes for ALS, risk factors and modifiers. This leads to an improved genotype/phenotype correlation and is becoming increasingly relevant for genetic diagnosis, counseling and therapy. The first gene-specific therapies are being tested in ongoing clinical trials. Consequently, this review aims to summarize the most important ...
Source: Current Opinion in Neurology - Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Albert C. Ludolph Source Type: research
Abstract Paget's disease of bone (PDB) is a focal bone disorder affecting the skeleton segmentally. A strong genetic component has been shown in PDB, and variants in several genes, such as SQSTM1, VCP, and OPTN, have been associated with the disease. Mutations in the same genes have also been reported in patients with frontotemporal dementia and amyotrophic lateral sclerosis. Hexanucleotide repeat expansions in the C9ORF72 gene have been shown to be responsible for both familial and sporadic frontotemporal dementia/amyotrophic lateral sclerosis. Thence, we evaluated the frequency of the C9ORF72 hexanucleotide repe...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research
Amyotrophic lateral sclerosis (ALS) is usually sporadic, but 20% of European ancestry cases have a family history of ALS or frontotemporal dementia (FTD) [1]. More than 30 genes confer a higher risk for ALS, and C9orf72, TARDBP, SOD1 and FUS account for nearly 70% of all familial (fALS) cases [1]. Tank-binding kinase 1 (TBK1) is an established causal gene associated with 1% of fALS and/or FTD [2]. It codes for a multifunctional kinase involved in multiple cellular processes, such as neuroinflammation and autophagy [3].
Source: Journal of the Neurological Sciences - Category: Neurology Authors: Tags: Letter to the Editor Source Type: research
Abstract A shared neuropathological hallmark in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is nuclear clearance and cytoplasmic aggregation of TARDBP/TDP-43 (TAR DNA binding protein). We previously showed that the ability of TARDBP to repress nonconserved cryptic exons was impaired in brains of patients with ALS and FTD, suggesting that its nuclear depletion contributes to neurodegeneration. However, the critical pathways impacted by the failure to repress cryptic exons that may contribute to neurodegeneration remain undefined. Here, we report that transcriptome analysis of TARDBP-defici...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research
Conclusion and Perspectives The ARE has been studied for a long time, and about 20 ARE-BPs have been identified since discovery of first ARE-BP, AUF1 (Brewer, 1991; Garcia-Maurino et al., 2017). The specific target mRNAs for different ARE-BPs, as well as their molecular functions on these mRNAs, and contribution of this regulation to specific biological processes are gradually being uncovered. However, with a few exceptions, the molecular mechanisms used by ARE-BPs to regulate their targets are still unknown. In particular, the mechanism to recognize and control specific targets from the large number of transcripts t...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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