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

2018 ◽  
Vol 18 (5-6) ◽  
pp. 310-314 ◽  
Author(s):  
Paola Origone ◽  
Alessandro Geroldi ◽  
Merit Lamp ◽  
Francesca Sanguineri ◽  
Claudia Caponnetto ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Lower Motor Neuron ◽  
Multiple Gene ◽  
C9orf72 Expansion ◽  
Mapt Gene ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Pure Motor

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.

scholarly journals RT2 PCR array screening reveals distinct perturbations in DNA damage response signaling in FUS-associated motor neuron disease

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Haibo Wang ◽  
Suganya Rangaswamy ◽  
Manohar Kodavati ◽  
Joy Mitra ◽  
Wenting Guo ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Dna Damage Response ◽  
Spinal Cord Tissue ◽  
Sporadic Als ◽  
Damage Response ◽  
Als Patients

AbstractAmyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease that has been linked to defective DNA repair. Many familial ALS patients harbor autosomal dominant mutations in the gene encoding the RNA/DNA binding protein ‘fused in sarcoma’ (FUS) commonly inducing its cytoplasmic mislocalization. Recent reports from our group and others demonstrate a role of FUS in maintaining genome integrity and the DNA damage response (DDR). FUS interacts with many DDR proteins and may regulate their recruitment at damage sites. Given the role of FUS in RNA transactions, here we explore whether FUS also regulates the expression of DDR factors. We performed RT2 PCR arrays for DNA repair and DDR signaling pathways in CRISPR/Cas9 FUS knockout (KO) and shRNA mediated FUS knockdown (KD) cells, which revealed significant (> 2-fold) downregulation of BRCA1, DNA ligase 4, MSH complex and RAD23B. Importantly, similar perturbations in these factors were also consistent in motor neurons differentiated from an ALS patient-derived induced pluripotent stem cell (iPSC) line with a FUS-P525L mutation, as well as in postmortem spinal cord tissue of sporadic ALS patients with FUS pathology. BRCA1 depletion has been linked to neuronal DNA double-strand breaks (DSBs) accumulation and cognitive defects. The ubiquitin receptor RAD23 functions both in nucleotide excision repair and proteasomal protein clearance pathway and is thus linked to neurodegeneration. Together, our study suggests that the FUS pathology perturbs DDR signaling via both its direct role and the effect on the expression of DDR genes. This underscors an intricate connections between FUS, genome instability, and neurodegeneration.

Motor Neuron Disease (DRAFT)

2018 ◽  
Author(s):  
Tamara Kaplan ◽  
Tracey Milligan
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Muscular Atrophy ◽  
Lower Motor Neuron ◽  
Lateral Sclerosis

The video in this chapter explores motor neuron disease, including amytrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). It discusses the signs of upper motor neuron (UMN) and lower motor neuron (LMN) pathology, as well as Kennedy disease.

scholarly journals Wetherbee Ail

1974 ◽  
Vol 1 (2) ◽  
pp. 139-140 ◽  
Author(s):  
James M. Powers ◽  
Dikran S. Horoupian ◽  
Herbert H. Schaumburg
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Neuronal Loss ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Spinocerebellar Degeneration ◽  
Lateral Column ◽  
Intracytoplasmic Inclusions ◽  
Lateral Sclerosis

SUMMARYThe neuropathological findings of a Farr family member consist of neuronal loss in the anterior horns and dorsal nuclei of Clarke, neuronal intracytoplasmic inclusions and posterior and lateral column demyelination. This report supports the role of familial amyotrophic lateral sclerosis as a link between common motor neuron disease and classical spinocerebellar degeneration.

scholarly journals Role of neuro-sonography of peripheral nerves as a diagnostic and a differentiation tool of amyotrophic lateral sclerosis

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Rana Zakaria Ahmed Mohamed ◽  
Haitham Hamdy Salem ◽  
Hossam Moussa El-Sayed Sakr ◽  
Hossam-Eldin Mahmoud Afifi ◽  
Ahmed Mohammed Elsadek ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Differential Diagnosis ◽  
Early Diagnosis ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Neurodegenerative Disorders ◽  
Peripheral Nerves ◽  
Radiological Criteria ◽  
Lateral Sclerosis

Abstract Background Motor neuron disease is a heterogeneous group of progressive neurodegenerative disorders, most common of which is amyotrophic lateral sclerosis (ALS). There are many clinical and radiological criteria to diagnose amyotrophic lateral sclerosis and to differentiate it from other motor neuron disease and neurodegenerative disorders. Neuro-sonography is one of the easily applied tools to diagnose and differentiate ALS. ALS diagnosis is delayed up to 3 years according to some authors due to the wide differential diagnosis, with cervical degeneration being a common misdiagnosis. The objective of this study was to evaluate the role of neuro-sonography in diagnosis and differentiation of amyotrophic lateral sclerosis from other causes of progressive mixed upper and lower motor neuron lesion. Results A total neuro-sonography score at a cut-off point (≤ 127) predicted patients with ALS, with good (85%) accuracy, sensitivity = 73% and specificity = 83% (p < 0.01) and Lt median arm score at a cut-off point (≤ 6) predicted patients with ALS, with good (88%) accuracy, sensitivity = 86% and specificity = 86% (p < 0.01) and the median nerve at the arm level was the most sensitive and specific nerve to predict patients with ALS. Conclusion Neuro-sonography of peripheral nerves is a recent, noninvasive, accessible technique that can be used in early diagnosis of ALS.

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