FUS mutations in sporadic amyotrophic lateral sclerosis: Clinical and genetic analysis

Sproviero, William; Bella, Vincenzo La; Mazzei, R.; Valentino, Paola; Rodolico, Carmelo; Simone, I. L.; Logroscino, Giancarlo; Ungaro, C; Magariello, A.; Patitucci, A; Tedeschi, Gioacchino; Spataro, Rossella; Condino, Francesca; Bono, Francesco; Citrigno, Luigi; Monsurrò, Maria Rosaria; Muglia, M.; Gambardella, Antonio; Quattrone, Aldo; Conforti, Francesca Luisa

doi:10.1016/j.neurobiolaging.2011.10.005

Cited by 34 publications

(14 citation statements)

References 20 publications

(28 reference statements)

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“…Therefore, we speculate that the high signal intensities of the corticospinal tracts on the DWI image in the present case reflect a rapid degeneration of the UMN and the corticospinal tracts, which is not a common finding in ALS cases with an FUS gene mutation. No specific findings, including abnormal signal intensities of the corticospinal tracts, have been reported on cerebral MRI of ALS cases with an FUS gene mutation (8,24,27). The present case also exhibited mild frontal lobe atrophy on MRI, as well as reduced cerebral blood flow in the bilateral frontal lobe areas according to the 99m Tc-ECD SPECT analysis.…”

Section: Discussionmentioning

confidence: 42%

Juvenile-onset Sporadic Amyotrophic Lateral Sclerosis with a Frameshift <i>FUS</i> Gene Mutation Presenting Unique Neuroradiological Findings and Cognitive Impairment

et al. 2016

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A 24-year-old Japanese woman developed anterocollis, weakness of the proximal arms, and subsequent cognitive impairment. A neurological examination revealed amyotrophic lateral sclerosis (ALS) without a family history. Systemic muscle atrophy progressed rapidly. Cerebral MRI clearly exhibited high signal intensities along the bilateral pyramidal tracts. An analysis of the FUS gene revealed a heterozygous two-base pair deletion, c.1507-1508delAG (p.G504WfsX515). A subset of juvenile-onset familial/sporadic ALS cases with FUS gene mutations reportedly demonstrates mental retardation or learning difficulty. Our study emphasizes the importance of conducting a FUS gene analysis in juvenile-onset ALS cases, even when no family occurrence is confirmed.

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Section: Discussionmentioning

confidence: 42%

Juvenile-onset Sporadic Amyotrophic Lateral Sclerosis with a Frameshift <i>FUS</i> Gene Mutation Presenting Unique Neuroradiological Findings and Cognitive Impairment

et al. 2016

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“…Although FUS mutations were not found in sALS patients, this is probably due to both the selective detection of exons in mutational hotspot regions and the use of small sample sizes. Zou ZY reported that FUS mutations could be present in approximately 1.0% of northern Chinese sALS patients, which is similar to the 1.6% mutation frequency found in Korean patients and the 1.25% mutation frequency found Italian patients12141920. With regards to the frequency of TARDBP mutation, it appears that the frequency of TARDBP mutations in Caucasian populations (Italy: 2.7%; France and Quebec: 4.5%) was higher than that in Asian populations21222324.…”

Section: Discussionmentioning

confidence: 60%

Screening of SOD1, FUS and TARDBP genes in patients with amyotrophic lateral sclerosis in central-southern China

Hou

Jiao

Xiao

et al. 2016

Sci Rep

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons of the brain, brainstem and spinal cord. To date, mutations in more than 30 genes have been linked to the pathogenesis of ALS. Among them, SOD1, FUS and TARDBP are ranked as the three most common genes associated with ALS. However, no mutation analysis has been reported in central-southern China. In this study, we sequenced SOD1, FUS and TARDBP in a central-southern Chinese cohort of 173 patients with ALS (15 familial ALS and 158 sporadic ALS) to detect mutations. As a result, five missense mutations in SOD1, namely, p.D101N, p.D101G, p.C111Y, p.N86S and p.V87A, were identified in three unrelated familial probands and three sporadic cases; two mutations in FUS were found in two unrelated familial probands, including an insertion mutation (p.P525_Y526insY) and a missense mutation (p.R521H); no variants of TARDBP were observed in patients. Therefore, SOD1 mutations were present in 20.0% of familial ALS patients and 1.9% of sporadic ALS patients, while FUS mutations were responsible for 13.3% of familial ALS cases, and TARDBP mutations were rare in either familial or sporadic ALS cases. This study broadens the known mutational spectrum in patients with ALS and further demonstrates the necessity for genetic screening in ALS patients from central-southern China.

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“…The first two reports suggested that FUS mutations might only be associated with FALS [Kwiatkowski et al, ; Vance et al, ]. However, several recent reports identified FUS mutations in SALS patients, including the most common variants p.R521C and p.R521H (Table ) [Belzil et al, ; Blair et al, ; Broustal et al, ; Chiò et al, ; Corrado et al, ; Drepper et al, ; Groen et al, ; Kwiatkowski et al, ; Lai et al, ; Millecamps et al, ; Rademakers et al, ; Sproviero et al, ; Suzuki et al, ; Syriani et al, ; Ticozzi et al, ; Tsai et al, ; van Blitterswijk et al, ; Vance et al, ; Van Damme et al, ; Van Langenhove et al, ; Yamamoto‐Watanabe et al, ; Yan et al, ; Zou et al, ].…”

Section: Fus Mutations In Alsmentioning

confidence: 99%

TARDBPandFUSMutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update

2013

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Mutations in the TAR DNA Binding Protein gene (TARDBP), encoding the protein TDP-43, were identified in amyotrophic lateral sclerosis (ALS) patients. Interestingly, TDP-43 positive inclusion bodies were first discovered in ubiquitin-positive, tau-negative ALS and frontotemporal dementia (FTD) inclusion bodies, and subsequently observed in the majority of neurodegenerative disorders. To date, 47 missense and one truncating mutations have been described in a large number of familial (FALS) and sporadic (SALS) patients. Fused in sarcoma (FUS) was found to be responsible for a previously identified ALS6 locus, being mutated in both FALS and SALS patients. TARDBP and FUS have a structural and functional similarity and most of mutations in both genes are also clustered in the C-terminus of the proteins. The molecular mechanisms through which mutant TDP-43 and FUS may cause motor neuron degeneration are not well understood. Both proteins play an important role in mRNA transport, axonal maintenance, and motor neuron development. Functional characterization of these mutations in in vitro and in vivo systems is helping to better understand how motor neuron degeneration occurs. This report summarizes the biological and clinical relevance of TARDBP and FUS mutations in ALS. All the data reviewed here have been submitted to a database based on the Leiden Open (source) Variation Database (LOVD) and is accessible online at www.lovd.nl/TARDBP, www.lovd.nl/FUS.

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FUS mutations in sporadic amyotrophic lateral sclerosis: Clinical and genetic analysis

Cited by 34 publications

References 20 publications

Juvenile-onset Sporadic Amyotrophic Lateral Sclerosis with a Frameshift <i>FUS</i> Gene Mutation Presenting Unique Neuroradiological Findings and Cognitive Impairment

Juvenile-onset Sporadic Amyotrophic Lateral Sclerosis with a Frameshift <i>FUS</i> Gene Mutation Presenting Unique Neuroradiological Findings and Cognitive Impairment

Screening of SOD1, FUS and TARDBP genes in patients with amyotrophic lateral sclerosis in central-southern China

TARDBPandFUSMutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update

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