Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder. Ten percent of cases are inherited; most involve unidentified genes. We report here 13 mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene on chromosome 16 that were specific for familial ALS. The FUS/TLS protein binds to RNA, functions in diverse processes, and is normally located predominantly in the nucleus. In contrast, the mutant forms of FUS/TLS accumulated in the cytoplasm of neurons, a pathology that is similar to that of the gene TAR DNA-binding protein 43 (TDP43), whose mutations also cause ALS. Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.

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References

Articles referenced by this article (22)

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AUTHOR UNKNOWN
Gene 1998
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https://en.wikipedia.org/wiki/FUS_(gene)

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Diseases in OMIM (2)

AMYOTROPHIC LATERAL SCLEROSIS 6 WITH OR WITHOUT FRONTOTEMPORAL DEMENTIA;(OMIM - 608030)
FUSED IN SARCOMA; FUS(OMIM - 137070)

Proteins in UniProt

RNA-binding protein FUS(UniProt - P35637)

GlyGen is an international glycobioinformatics knowledgebase funded by The National Institutes of Health to facilitate glycoscience research by integrating diverse kinds of information, including glycomics, genomics, proteomics (and glycoproteomics), cell biology, developmental biology and biochemistry.

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Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.

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References

Epidemiology of ALS.

Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis.

TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis.

TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis.

TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis.

Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.

Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis.

Identification of an RNA binding specificity for the potential splicing factor TLS.

Title not supplied

Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation.

Citations & impact

Impact metrics

Citations of article over time

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Article citations

Exercise, disease state and sex influence the beneficial effects of Fn14-depletion on survival and muscle pathology in the SOD1<sup>G93A</sup> amyotrophic lateral sclerosis (ALS) mouse model.

Transcript errors generate amyloid-like proteins in huwman cells.

Hippocampal aggregation signatures of pathogenic UBQLN2 in amyotrophic lateral sclerosis and frontotemporal dementia.

The roles of TAF1 in neuroscience and beyond.

Microglial senescence in neurodegeneration: Insights, implications, and therapeutic opportunities.

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Wikipedia

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Data that cites the article

Diseases in OMIM (2)

Proteins in UniProt

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Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.

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