Novel TARDBP missense mutation caused familial amyotrophic lateral sclerosis with frontotemporal dementia and parkinsonism

Amyotrophic lateral sclerosis represents the most common neurodegenerative disease leading to upper and lower motor neuron compromise. Although the vast majority of cases are sporadic, substantial gain has been observed in the knowledge of the genetic forms of the disease, especially of familial forms. There is a direct correlation between the profile of the mutated genes in sporadic and familial forms, highlighting the main role ofC9orf72 gene in the clinical forms associated with frontotemporal dementia spectrum. The different genes related to familial and sporadic forms represent an important advance on the pathophysiology of the disease and genetic therapeutic perspectives, such as antisense therapy. The objective of this review is to signal and summarize clinical and genetic data related to familial forms of amyotrophic lateral sclerosis.

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A familial amyotrophic lateral sclerosis pedigree discordant for a novel p.Glu46Asp heterozygous OPTN variant and the p.Ala5Val heterozygous SOD1 missense mutation

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2020.03.032 ◽

2020 ◽

Vol 75 ◽

pp. 223-225

Author(s):

Antonio Canosa ◽

Maurizio Grassano ◽

Marco Barberis ◽

Maura Brunetti ◽

Umberto Manera ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Missense Mutation ◽

Familial Amyotrophic Lateral Sclerosis ◽

Lateral Sclerosis

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Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2–21.3

Brain ◽

10.1093/brain/awl030 ◽

2006 ◽

Vol 129 (4) ◽

pp. 868-876 ◽

Cited By ~ 260

Author(s):

Caroline Vance ◽

Ammar Al-Chalabi ◽

Deborah Ruddy ◽

Bradley N. Smith ◽

Xun Hu ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Frontotemporal Dementia ◽

Familial Amyotrophic Lateral Sclerosis ◽

Lateral Sclerosis

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Transgenic mouse model for familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation

Neuropathology ◽

10.1046/j.1440-1789.2001.00361.x ◽

2001 ◽

Vol 21 (1) ◽

pp. 82-92 ◽

Cited By ~ 72

Author(s):

Noriyuki Shibata

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Superoxide Dismutase ◽

Mouse Model ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Familial Amyotrophic Lateral Sclerosis ◽

Superoxide Dismutase 1 ◽

Lateral Sclerosis

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389. Engineered microRNAs Against a C9ORF72 Transgenic Mouse Model To Treat Human Familial Amyotrophic Lateral Sclerosis (FALS)

Molecular Therapy ◽

10.1016/s1525-0016(16)35402-8 ◽

2014 ◽

Vol 22 ◽

pp. S148

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Mouse Model ◽

Transgenic Mouse ◽

Transgenic Mouse Model ◽

Familial Amyotrophic Lateral Sclerosis ◽

Lateral Sclerosis

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The densitometric physical fractionator for counting neuronal populations: application to a mouse model of familial amyotrophic lateral sclerosis

Journal of Neuroscience Methods ◽

10.1016/s0165-0270(03)00201-2 ◽

2003 ◽

Vol 129 (1) ◽

pp. 61-71 ◽

Cited By ~ 9

Author(s):

Giuseppe Luca Ciavarro ◽

Novella Calvaresi ◽

Andrea Botturi ◽

Caterina Bendotti ◽

Giuseppe Andreoni ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Mouse Model ◽

Familial Amyotrophic Lateral Sclerosis ◽

Neuronal Populations ◽

Lateral Sclerosis

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Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers

Brain ◽

10.1093/brain/awu249 ◽

2014 ◽

Vol 137 (11) ◽

pp. 2938-2950 ◽

Cited By ~ 49

Author(s):

Axel Freischmidt ◽

Kathrin Müller ◽

Lisa Zondler ◽

Patrick Weydt ◽

Alexander E. Volk ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Expression Profiles ◽

Consensus Sequence ◽

Disease Onset ◽

Therapeutic Targets ◽

Familial Amyotrophic Lateral Sclerosis ◽

Sequence Motif ◽

Mutation Carriers ◽

Disease Modifying ◽

Lateral Sclerosis

Abstract Knowledge about the nature of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis is largely lacking. It could not only pave the way for the discovery of valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained comprehensive expression profiles of microRNAs in the serum of patients with familial amyotrophic lateral sclerosis, asymptomatic mutation carriers and healthy control subjects. We observed a strikingly homogenous microRNA profile in patients with familial amyotrophic lateral sclerosis that was largely independent from the underlying disease gene. Moreover, we identified 24 significantly downregulated microRNAs in pre-manifest amyotrophic lateral sclerosis mutation carriers up to two decades or more before the estimated time window of disease onset; 91.7% of the downregulated microRNAs in mutation carriers overlapped with the patients with familial amyotrophic lateral sclerosis. Bioinformatic analysis revealed a consensus sequence motif present in the vast majority of downregulated microRNAs identified in this study. Our data thus suggest specific common denominators regarding molecular pathogenesis of different amyotrophic lateral sclerosis genes. We describe the earliest pathomolecular alterations in amyotrophic lateral sclerosis mutation carriers known to date, which provide a basis for the discovery of novel therapeutic targets and strongly argue for studies evaluating presymptomatic disease-modifying treatment in amyotrophic lateral sclerosis.

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