<i>FUS</i>
            gene mutation in amyotrophic lateral sclerosis: a new case report and systematic review

Xiao, Xin; Li, Min; Ye, Zhi; He, Xiaoyan; Wei, Jun; Zha, Yunhong

doi:10.1080/21678421.2023.2272170

Cited by 4 publications

(4 citation statements)

References 84 publications

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“…We also found 11 genetic variations in exons 2, 3 and 6: 8 missense, 2 silent and 1 nonsense variant. It is very interesting that most studies are referring to variants located in exons 14-15 [21], while in our study, we found none in these exons. This suggests that the genetic basis of the Greek sALS patients has a unique pattern, consistent with our previous findings.…”

Section: Discussioncontrasting

confidence: 68%

“…The concentration and quality of the DNA assessed using Nanodrop 2000 (Thermo Fisher Scientific, Waltham, MA, USA) and 50 ng of genomic DNA was used, through Polymerase Chain Reaction (PCR), to amplify 17 DNA fragments [4 fragments including exons 2–5 of SOD1 (NM_000454.5, hg_38), 7 fragments including exons 2, 3, 5, 6, 12–15 and the 3′UTR of FUS (NM_004960.4, hg_38) and 6 fragments including exons 1–6 of the TARDBP gene (NM_007375.4, hg_38)]. The selection of these segments for analysis was based on the fact that these are the exons in which more disease-associated variants have been identified [ 21 , 36 ]. The amplification conditions and primer sequences are available upon request.…”

Section: Methodsmentioning

confidence: 99%

“…4, hg_38)]. The selection of these segments for analysis was based on the fact that these are the exons in which more disease-associated variants have been identified [21,36]. The amplification conditions and primer sequences are available upon request.…”

Section: Genetic Testingmentioning

confidence: 99%

“…Another gene that is strongly associated with ALS is FUS , also known as translocated in liposarcoma (TLS), which encodes a protein involved in RNA processing. More than 170 genomic variants have been identified, most of them missense [ 21 ], and are associated with approximately 5% of fALS [ 22 ] and 0.3% of sALS cases [ 23 ]. It has been reported that patients with FUS variants have an earlier onset of symptoms than other forms of the disease, usually before the age of 45 years [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

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Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients

Ivantsik,

John,

Kydonopoulou

et al. 2024

Genes

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Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease that affects motor neurons, leading to paralysis and death usually 3–5 years after the onset of symptoms. The investigation of both sporadic and familial ALS highlighted four main genes that contribute to the pathogenesis of the disease: SOD1, FUS, TARDBP and C9orf72. This study aims to provide a comprehensive investigation of genetic variants found in SOD1, FUS and TARDBP genes in Greek sporadic ALS (sALS) cases. Our sequencing analysis of the coding regions of the abovementioned genes that include the majority of the variants that lead to ALS in 32 sALS patients and 3 healthy relatives revealed 6 variants in SOD1, 19 variants in FUS and 37 variants in TARDBP, of which the SOD1 p.D90A and the FUS c.*356G>A (rs886051940) variants have been previously associated with ALS, while two novel nonsense pathogenic variants were also identified, namely FUS p.R241* and TDP-43 p.Y214*. Our study contributes to the worldwide effort toward clarifying the genetic basis of sALS to better understand the disease’s molecular pathology.

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Section: Discussioncontrasting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Section: Genetic Testingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients

Ivantsik,

John,

Kydonopoulou

et al. 2024

Genes

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Expression pattern of the fused in sarcoma gene and its contextual influence on the density-specific response of the growth hormone/insulin-like growth factor 1 axis in zig-zag eels (Mastacembelus armatus)

Xue,

Gao,

Zhang

et al. 2024

Front. Mar. Sci.

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The fused in sarcoma (FUS) protein is a DNA/RNA binding protein from the ten-eleven translocation protein family that is associated with neurodegeneration, and it has been shown to promote cell proliferation through the growth hormone/insulin-like growth factor 1 (Gh/Igf-1) signaling pathway. The zig-zag eel (Mastacembelus armatus) is a newly discovered species exhibiting sexual dimorphism in growth, and the potential role of fus in the growth and development of this species remains largely unknown. Herein, we analyzed the homology, conserved domains, evolutionary characteristics, and conserved syntenies of fus in several teleost species. The expression of fus was predominant in the brain and exhibited sexual dimorphism in the brain, muscle, and liver of zig-zag eels. We found that microRNA (miR)-146-5p, miR-489-3p, and 24 other miRNAs were targeted to the fus 3′ untranslated region, which might affect muscle and bone development in adults. The igf1, insulin-like growth factor 1 receptor a (igf1ra), insulin-like growth factor 2 receptor (igf2r), growth hormone-releasing hormone-like receptor (ghrhrl), growth hormone secretagogue receptor type 1 (ghsr), and glucocorticoid receptor (gr) genes contained a higher abundance of GU-rich fus motifs compared to the other four genes analyzed in zig-zag eels. We also measured the expression of fus mRNA during fish culture at various stocking densities to further elucidate the relationship between fus expression and the Gh/Igf-1 axis. After 100 days of fish cultivation, the expression of fus and ghrhrl decreased and the expression of ghrh and gr increased as the culture density increased (p < 0.05). The expression of fus exhibited a remarkable positive correlation with a specific growth rate. These results indicate that fus mediates growth differences by regulating the expression of several growth-related genes including Gh/Igf-1 axis genes in zig-zag eels.

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Allele-Selective Thiomorpholino Antisense Oligonucleotides as a Therapeutic Approach for Fused-in-Sarcoma Amyotrophic Lateral Sclerosis

Mejzini,

Caruthers,

Schafer

et al. 2024

IJMS

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Pathogenic variations in the fused in sarcoma (FUS) gene are associated with rare and aggressive forms of amyotrophic lateral sclerosis (ALS). As FUS-ALS is a dominant disease, a targeted, allele-selective approach to FUS knockdown is most suitable. Antisense oligonucleotides (AOs) are a promising therapeutic platform for treating such diseases. In this study, we have explored the potential for allele-selective knockdown of FUS. Gapmer-type AOs targeted to two common neutral polymorphisms in FUS were designed and evaluated in human fibroblasts. AOs had either methoxyethyl (MOE) or thiomorpholino (TMO) modifications. We found that the TMO modification improved allele selectivity and efficacy for the lead sequences when compared to the MOE counterparts. After TMO-modified gapmer knockdown of the target allele, up to 93% of FUS transcripts detected were from the non-target allele. Compared to MOE-modified AOs, the TMO-modified AOs also demonstrated reduced formation of structured nuclear inclusions and SFPQ aggregation that can be triggered by phosphorothioate-containing AOs. How overall length and gap length of the TMO-modified AOs affected allele selectivity, efficiency and off-target gene knockdown was also evaluated. We have shown that allele-selective knockdown of FUS may be a viable therapeutic strategy for treating FUS-ALS and demonstrated the benefits of the TMO modification for allele-selective applications.

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FUS gene mutation in amyotrophic lateral sclerosis: a new case report and systematic review

Cited by 4 publications

References 84 publications

Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients

Novel Pathogenic Variants Leading to Sporadic Amyotrophic Lateral Sclerosis in Greek Patients

Expression pattern of the fused in sarcoma gene and its contextual influence on the density-specific response of the growth hormone/insulin-like growth factor 1 axis in zig-zag eels (Mastacembelus armatus)

Allele-Selective Thiomorpholino Antisense Oligonucleotides as a Therapeutic Approach for Fused-in-Sarcoma Amyotrophic Lateral Sclerosis

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