Journal ArticleDOI
Identification of novel FUS mutations in sporadic cases of amyotrophic lateral sclerosis.
Veronique V. Belzil,Hussein Daoud,Judith St-Onge,Anne Desjarlais,Jean-Pierre Bouchard,Nicolas Dupré,Lucette Lacomblez,François Salachas,Pierre-François Pradat,Vincent Meininger,William Camu,Patrick A. Dion,Guy A. Rouleau +12 more
Reads0
Chats0
TLDR
FUS gene mutations are rare in SALS, with four new FUS variants identified in five different SALS cases, two of which are located in the carboxy terminal of the protein where the previously reported variants were mostly clustered.Abstract:
Mutations in the FUS gene have been recently associated with amyotrophic lateral sclerosis (ALS). While most of the variants have been identified in patients with a family history of the disease, a few mutations were also found in sporadic patients. Considering this, we wanted to evaluate the frequency of mutations in the coding region of the FUS gene in a sporadic ALS (SALS) cohort compared to a control population. We tested 475 SALS cases of European origin and 475 matched controls for coding variations in the 15 exons of the FUS gene. Rare novel variants were identified in a total of five SALS patients: one missense, one deletion, one frameshift, and one nonsense substitution. Two of the four variants are located in the carboxy terminal of the protein where the previously reported variants were mostly clustered. In conclusion, FUS gene mutations are rare in SALS, with four new FUS variants identified in five different SALS cases. These findings will help evaluate the proportion of FUS variation...read more
Citations
More filters
Journal ArticleDOI
RNA-binding proteins with prion-like domains in health and disease
TL;DR: The physiological and pathological roles of the most prominent RBPs with PrLDs are reviewed and the potential of protein disaggregases, including Hsp104, as a therapeutic strategy to combat the aberrant phase transitions of RBP with Pr LDs that likely underpin neurodegeneration are highlighted.
Journal ArticleDOI
The role of FUS gene variants in neurodegenerative diseases
Hao Deng,Kai Gao,Joseph Jankovic +2 more
TL;DR: Current understanding of the normal function of FUS is summarized, its role in the pathology of ALS, FTLD, essential tremor and other neurodegenerative diseases is described, and comments on the underlying pathogenetic mechanisms are included.
Journal ArticleDOI
ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules
Caroline Vance,Emma L. Scotter,Agnes L. Nishimura,Claire Troakes,Jacqueline C. Mitchell,Claudia Kathe,Hazel Urwin,Catherine Manser,Christopher C.J. Miller,Tibor Hortobágyi,Mike Dragunow,Boris Rogelj,Christopher Shaw +12 more
TL;DR: It is demonstrated that C-terminal ALS mutations disrupt the nuclear localizing signal (NLS) of FUS resulting in cytoplasmic accumulation in transfected cells and patient fibroblasts, and this findings support a two-hit hypothesis, whereby cytopLasmic mislocalization of F US protein, followed by cellular stress, contributes to the formation of cytopal aggregates that may sequester FUS, disrupt RNA processing and initiate motor neuron degeneration.
Journal ArticleDOI
Exome Sequencing Identifies FUS Mutations as a Cause of Essential Tremor
Nancy D. Merner,Simon Girard,Hélène Catoire,Cynthia V. Bourassa,Veronique V. Belzil,Jean-Baptiste Rivière,Pascale Hince,Annie Levert,Alexandre Dionne-Laporte,Dan Spiegelman,Anne Noreau,Sabrina Diab,Anna Szuto,Helene Fournier,John Verner Raelson,Majid Belouchi,Michel Panisset,Patrick Cossette,Nicolas Dupré,Geneviève Bernard,Sylvain Chouinard,Patrick A. Dion,Guy A. Rouleau +22 more
TL;DR: Exome sequencing is used to implement a simple approach to control for misdiagnosis of ET, as well as phenocopies involving sporadic and senile ET cases, and it is shown that the ET FUS nonsense mutation is degraded by the nonsense-mediated-decay pathway, whereas amyotrophic lateral sclerosis FUS mutant transcripts are not.
Journal ArticleDOI
ALS/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS
Jone López-Erauskin,Takahiro Tadokoro,Michael Baughn,Brian Myers,Melissa McAlonis-Downes,Carlos Chillon-Marinas,Joshua N. Asiaban,Jonathan W. Artates,Anh Bui,Anne P. Vetto,Sandra K. Lee,Ai Vy Le,Ying Sun,Mélanie Jambeau,Jihane Boubaker,Deborah A. Swing,Jinsong Qiu,Geoffrey G. Hicks,Zhengyu Ouyang,Xiang-Dong Fu,Lino Tessarollo,Shuo-Chien Ling,Philippe A. Parone,Christopher Shaw,Christopher Shaw,Martin Marsala,Clotilde Lagier-Tourenne,Don W. Cleveland,Sandrine Da Cruz +28 more
TL;DR: Evidence demonstrates that human ALS/FTD-linked mutations in FUS induce a gain of toxicity that includes stress-mediated suppression in intra-axonal translation, synaptic dysfunction, and progressive age-dependent motor and cognitive disease without cytoplasmic aggregation, altered nuclear localization, or aberrant splicing of FUS-bound pre-mRNAs.
References
More filters
Journal ArticleDOI
Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
Manuela Neumann,Deepak M. Sampathu,Linda K. Kwong,Adam C. Truax,Matthew Micsenyi,Thomas T. Chou,Jennifer Bruce,Theresa Schuck,Murray Grossman,Christopher M. Clark,Leo McCluskey,Bruce L. Miller,Eliezer Masliah,Ian R. A. Mackenzie,Howard Feldman,Wolfgang Feiden,Hans A. Kretzschmar,John Q. Trojanowski,Virginia M.-Y. Lee +18 more
TL;DR: It is shown that TDP-43 is the major disease protein in both frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis.
Journal ArticleDOI
Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.
Thomas J. Kwiatkowski,D. A. Bosco,D. A. Bosco,A. L. LeClerc,A. L. LeClerc,Eric Tamrazian,Charles R. Vanderburg,Carsten Russ,Carsten Russ,A. Davis,James M. Gilchrist,E. J. Kasarskis,Theodore L. Munsat,Paul N. Valdmanis,Guy A. Rouleau,Betsy A. Hosler,Pietro Cortelli,P. J. De Jong,Yuko Yoshinaga,Jonathan L. Haines,Margaret A. Pericak-Vance,Jianhua Yan,Nicola Ticozzi,Nicola Ticozzi,Nicola Ticozzi,Teepu Siddique,Diane McKenna-Yasek,Peter C. Sapp,Peter C. Sapp,H R Horvitz,John Landers,John Landers,Robert H. Brown,Robert H. Brown +33 more
TL;DR: Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.
Journal ArticleDOI
Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6
Caroline Vance,Boris Rogelj,Tibor Hortobágyi,Kurt J. De Vos,Agnes L. Nishimura,Jemeen Sreedharan,Xun Hu,Bradley N. Smith,Deborah Ruddy,Paul Wright,Jeban Ganesalingam,Kelly L. Williams,Vineeta B. Tripathi,Safa Al-Saraj,Ammar Al-Chalabi,P. Nigel Leigh,Ian P. Blair,Garth A. Nicholson,Garth A. Nicholson,Jackie de Belleroche,Jean-Marc Gallo,Christopher C.J. Miller,Christopher C.J. Miller,Christopher Shaw +23 more
TL;DR: A missense mutation in the gene encoding fused in sarcoma (FUS) in a British kindred, linked to ALS6, is identified, which suggests that a common mechanism may underlie motor neuron degeneration.
Journal ArticleDOI
TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis
Edor Kabashi,Paul N. Valdmanis,Patrick A. Dion,Dan Spiegelman,Brendan J. McConkey,Christine Vande Velde,Jean-Pierre Bouchard,Lucette Lacomblez,Ksenia Pochigaeva,François Salachas,Pierre-François Pradat,William Camu,Vincent Meininger,Nicolas Dupré,Nicolas Dupré,Guy A. Rouleau +15 more
TL;DR: Findings further corroborate that TDP-43 is involved in ALS pathogenesis and reports eight missense mutations in nine individuals—six from individuals with sporadic ALS and three from those with familial ALS (FALS)—and a concurring increase of a smaller T DP-43 product.
Journal ArticleDOI
Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene.
TL;DR: This review highlights recent epidemiologic, clinical-genetic, and neurochemical advances in understanding of sporadic amyotrophic lateral sclerosis (ALS) and their relationships to familial ALS caused by superoxide dismutase (SOD1) gene mutations.
Related Papers (5)
Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.
Thomas J. Kwiatkowski,D. A. Bosco,D. A. Bosco,A. L. LeClerc,A. L. LeClerc,Eric Tamrazian,Charles R. Vanderburg,Carsten Russ,Carsten Russ,A. Davis,James M. Gilchrist,E. J. Kasarskis,Theodore L. Munsat,Paul N. Valdmanis,Guy A. Rouleau,Betsy A. Hosler,Pietro Cortelli,P. J. De Jong,Yuko Yoshinaga,Jonathan L. Haines,Margaret A. Pericak-Vance,Jianhua Yan,Nicola Ticozzi,Nicola Ticozzi,Nicola Ticozzi,Teepu Siddique,Diane McKenna-Yasek,Peter C. Sapp,Peter C. Sapp,H R Horvitz,John Landers,John Landers,Robert H. Brown,Robert H. Brown +33 more
Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6
Caroline Vance,Boris Rogelj,Tibor Hortobágyi,Kurt J. De Vos,Agnes L. Nishimura,Jemeen Sreedharan,Xun Hu,Bradley N. Smith,Deborah Ruddy,Paul Wright,Jeban Ganesalingam,Kelly L. Williams,Vineeta B. Tripathi,Safa Al-Saraj,Ammar Al-Chalabi,P. Nigel Leigh,Ian P. Blair,Garth A. Nicholson,Garth A. Nicholson,Jackie de Belleroche,Jean-Marc Gallo,Christopher C.J. Miller,Christopher C.J. Miller,Christopher Shaw +23 more
Mutations of FUS gene in sporadic amyotrophic lateral sclerosis
Lucia Corrado,Roberto Del Bo,Barbara Castellotti,Antonia Ratti,Cristina Cereda,Silvana Penco,Gianni Sorarù,Yari Carlomagno,S. Ghezzi,Viviana Pensato,Claudia Colombrita,Stella Gagliardi,Lorena Cozzi,Valeria Orsetti,Michelangelo Mancuso,Gabriele Siciliano,Letizia Mazzini,Giacomo P. Comi,Cinzia Gellera,Mauro Ceroni,Sandra D'Alfonso,Vincenzo Silani +21 more