A Japanese ALS6 family with mutation R521C in the FUS/TLS gene: A clinical, pathological and genetic report

Yamamoto-Watanabe, Yukiko; Watanabe, Mitsunori; Okamoto, Koichi; Fujita, Yukio; Jackson, Mandy; Ikeda, Masaki; Nakazato, Yoichi; Ikeda, Yoshio; Matsubara, Etsuro; Kawarabayashi, Tatsuhiko; Shoji, Mikio

doi:10.1016/j.jns.2010.06.008

Cited by 36 publications

(26 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar phenotype was previously reported in some cases (11,(21)(22)(23)(24), and Ticozzi et al suggested that a certain FUS gene mutation may be associated with a specific clinical phenotype (21). The present case also showed a characteristic nonmotor symptom of cognitive impairment.…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 90%

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…The pathology was similar to our early-onset cases, with many BI in sensorimotor cortex and spinal cord, and FUS IHC demonstrating NCI but no GCI. Cases with adult-onset (range 28–69 years) have included several with the common p.R521C mutation [4, 15, 34 – 36, 38, 39] and others with p.R521G [18], p.R521H [8, 38], p.R524W [10] and p.G507N mutations [10]. With the exception of the p.G507N mutation case, all have had a family history of ALS.…”

Section: Discussionmentioning

confidence: 99%

“…These include sporadic and familial cases with both juvenile and adult-onset [1, 9, 12, 16 17, 33, 36]. Following the report that the BIBD subtype of FTLD was characterized by FUS-ir pathology [25], several cases of ALS with BI were re-evaluated [3, 6, 11, 15, 23, 34, 35, 39]. These studies demonstrated that the BI in cases of ALS are also consistently FUS-ir and that most [3, 11, 15, 34, 35, 39], but not all cases [11, 6, 23], are associated with a FUS mutation.…”

Section: Introductionmentioning

confidence: 99%

Pathological heterogeneity in amyotrophic lateral sclerosis with FUS mutations: two distinct patterns correlating with disease severity and mutation

et al. 2011

View full text Add to dashboard Cite

Mutations in the gene encoding the fused in sarcoma (FUS) protein are responsible for ~3% of familial amyotrophic lateral sclerosis (ALS) and <1% of sporadic ALS (ALS-FUS). Descriptions of the associated neuropathology are few and largely restricted to individual case reports. To better define the neuropathology associated with FUS mutations, we have undertaken a detailed comparative analysis of six cases of ALS-FUS that include sporadic and familial cases, with both juvenile and adult onset, and with four different FUS mutations. We found significant pathological heterogeneity among our cases, with two distinct patterns that correlated with the disease severity and the specific mutation. Frequent basophilic inclusions and round FUS-immunoreactive (FUS-ir) neuronal cytoplasmic inclusions (NCI) were a consistent feature of our early-onset cases, including two with the p.P525L mutation. In contrast, our late-onset cases, that included two with the p.R521C mutation, had tangle-like NCI and numerous FUS-ir glial cytoplasmic inclusions. Double-labeling experiments demonstrated that many of the glial inclusions were in oligodendrocytes. Comparison with the neuropathology of cases of frontotemporal lobar degeneration with FUS-ir pathology showed significant differences and suggests that FUS mutations are associated with a distinct pathobiology.

show abstract

“…However, relevant to this review, glial pathology is observed in all cases of familial and sporadic ALS (Neumann et al 2007;Nishihira et al 2008;Zhang et al 2008;Seilhean et al 2009;Hewitt et al 2010;Yamamoto-Watanabe et al 2010;Mackenzie et al 2011;Robertson et al 2011). Genes known to be linked to familial ALS are ubiquitously expressed, and ubiquitinated aggregates of ALScausing mutant proteins (such as SOD1 or TDP-43) are found in both neurons and glial cells (Bruijn et al 1997;Pasinelli et al 2000;Stieber et al 2000;Nishihira et al 2008;Zhang et al 2008;Forsberg et al 2011).…”

Section: Astrocytes In Alsmentioning

confidence: 99%

Astrocytes in Neurodegenerative Disease: Table 1.

Phatnani

Maniatis

2015

Cold Spring Harb Perspect Biol

340

242

View full text Add to dashboard Cite

A Japanese ALS6 family with mutation R521C in the FUS/TLS gene: A clinical, pathological and genetic report

Cited by 36 publications

References 30 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

Pathological heterogeneity in amyotrophic lateral sclerosis with FUS mutations: two distinct patterns correlating with disease severity and mutation

Astrocytes in Neurodegenerative Disease: Table 1.

Contact Info

Product

Resources

About