Correlation between low FAT1 expression and early affected muscle in facioscapulohumeral muscular dystrophy

@article{Mariot2015CorrelationBL,
  title={Correlation between low FAT1 expression and early affected muscle in facioscapulohumeral muscular dystrophy},
  author={Virginie Mariot and St{\'e}phane Roche and Christophe Hourde and D{\'e}bora Morueco Portilho and Sabrina Sacconi and Francesca Puppo and St{\'e}phanie Duguez and Philippe Rameau and Nathalie Caruso and Anne-lise Delezoide and Claude Desnuelle and Bettina Bessi{\`e}res and Sophie Collardeau and L{\'e}onard F{\'e}asson and Thierry Maisonobe and Fr{\'e}d{\'e}rique Magdinier and Françoise Helmbacher and Gillian S Butler-Browne and Vincent Mouly and Julie Dumonceaux},
  journal={Annals of Neurology},
  year={2015},
  volume={78}
}
Facioscapulohumeral muscular dystrophy (FSHD) is linked to either contraction of D4Z4 repeats on chromosome 4 or to mutations in the SMCHD1 gene, both of which result in the aberrant expression of the transcription factor DUX4. However, it is still difficult to correlate these genotypes with the phenotypes observed in patients. Because we have recently shown that mice with disrupted Fat1 functions exhibit FSHD‐like phenotypes, we have investigated the expression of the human FAT1 gene in FSHD. 
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DUX4 Signalling in the Pathogenesis of Facioscapulohumeral Muscular Dystrophy
TLDR
Studies on DUX4-affected pathways in skeletal muscle are reviewed and insights into how understanding these could help explain the unique pathogenesis of FSHD are provided.
FAT1 Gene Alteration in Facioscapulohumeral Muscular Dystrophy Type 1
TLDR
This study describes a 59-year-old woman with both contracted D4Z4 repeat units and a FAT1 mutation, and suggests that FAT1 alterations might work as a genetic modifier.
Facioscapulohumeral Muscular Dystrophy.
TLDR
Recent advances in understanding the pathophysiology of F SHD are described, including the application of MRI as a research and diagnostic tool, the genetic and epigenetic disruptions associated with the disease, and the molecular basis of FSHD.
Therapeutic Strategies Targeting DUX4 in FSHD
TLDR
Different research areas that are currently being considered to alter DUX4 expression and toxicity in muscle tissue and the cell and animal models designed to date are discussed.
Cellular and animal models for facioscapulohumeral muscular dystrophy
TLDR
Owing to its complex etiology and the toxicity of DUX4, modeling facioscapulohumeral muscular dystrophy (FSHD) is uniquely challenging, and the approaches that overcame these difficulties to develop highly relevant FSHD models are reviewed.
Facioscapulohumeral Muscular Dystrophy: Update on Pathogenesis and Future Treatments
TLDR
The underlying FSHD genetics, current understanding of the pathomechanism, and potential treatment strategies are reviewed, and the development of new clinical outcome measures as well as biomarkers, critical for the success of future clinical trials, are reviewed.
Facioscapulohumeral muscular dystrophy: genetics, gene activation and downstream signalling with regard to recent therapeutic approaches: an update
TLDR
There remains an incomplete understanding of the pathophysiology of FSHD in relation to the molecules leading to DUX4 gene activation and the downstream gene targets of Dux4 that cause its toxic effects.
Integrating clinical and genetic observations in facioscapulohumeral muscular dystrophy.
TLDR
An overview of the currently known key clinical and (epi)genetic aspects of facioscapulohumeral muscular dystrophy (FSHD) is given and perspectives to facilitate future research are provided.
Chromosome 10q-linked FSHD identifies DUX4 as principal disease gene
TLDR
This study shows that in rare situations, FSHD can occur on chromosome 10 due to an interchromosomal rearrangement with the F SHD locus on chromosome 4q, providing further evidence that DUX4 derepression is the dominant disease pathway for FSHd.
The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance.
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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