ArticleHuman molecular genetics2018
Smchd1 haploinsufficiency exacerbates the phenotype of a transgenic FSHD1 mouse model.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- SMCHD1 is a target for gene activation therapy to treat Prader-Willi syndrome.Science advances · 2026Article
- SMCHD1 Is Dispensable for Repeat-Induced FMR1 Hypermethylation in Fragile X Pluripotent Stem Cells.International journal of molecular sciences · 2026Article
- Prevalence and predictors of uncommon features in FSHD1 patients: insights from the French FSHD registry.Orphanet journal of rare diseases · 2025Article
- French National Protocol for diagnosis and care of facioscapulohumeral muscular dystrophy (FSHD).Journal of neurology · 2024Review
- Engineered FSHD mutations results in D4Z4 heterochromatin disruption and feedforward DUX4 network activation.iScience · 2024Article
- SMCHD1 has separable roles in chromatin architecture and gene silencing that could be targeted in disease.Nature communications · 2023Article
- Maternal SMCHD1 controls both imprinted Xist expression and imprinted X chromosome inactivation.Epigenetics & chromatin · 2022Article
- Epigenetic modifier SMCHD1 maintains a normal pool of long-term hematopoietic stem cells.iScience · 2022Article
- Genetic Approaches for the Treatment of Facioscapulohumeral Muscular Dystrophy.Frontiers in pharmacology · 2021Review
- Article
- Cellular and animal models for facioscapulohumeral muscular dystrophy.Disease models & mechanisms · 2020Review
- Dnmt3b regulates DUX4 expression in a tissue-dependent manner in transgenic D4Z4 mice.Skeletal muscle · 2020Article
- Therapeutic Strategies Targeting DUX4 in FSHD.Journal of clinical medicine · 2020Review
- Role of the Chromosome Architectural Factor SMCHD1 in X-Chromosome Inactivation, Gene Regulation, and Disease in Humans.Genetics · 2019Article
- AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD.JCI insight · 2018Article
- Facioscapulohumeral Muscular Dystrophy: Update on Pathogenesis and Future Treatments.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Review
- Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters.Nature structural & molecular biology · 2018Article
- Facioscapulohumeral dystrophy: activating an early embryonic transcriptional program in human skeletal muscle.Human molecular genetics · 2018Review
- A cre-inducible DUX4 transgenic mouse model for investigating facioscapulohumeral muscular dystrophy.PloS one · 2018Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
In humans, a copy of the DUX4 retrogene is located in each unit of the D4Z4 macrosatellite repeat that normally comprises 8-100 units. The D4Z4 repeat has heterochromatic features and does not express DUX4 in somatic cells. Individuals with facioscapulohumeral muscular dystrophy (FSHD) have a partial failure of somatic DUX4 repression resulting in the presence of DUX4 protein in sporadic muscle nuclei. Somatic DUX4 derepression is caused by contraction of the D4Z4 repeat to 1-10 units (FSHD1) or by heterozygous mutations in genes responsible for maintaining the D4Z4 chromatin structure in a repressive state (FSHD2). One of the FSHD2 genes is the structural maintenance of chromosomes hinge domain 1 (SMCHD1) gene. SMCHD1 mutations have also been identified in FSHD1; patients carrying a contracted D4Z4 repeat and a SMCHD1 mutation are more severely affected than relatives with only a contracted repeat or a SMCHD1 mutation. To evaluate the modifier role of SMCHD1, we crossbred mice carrying a contracted D4Z4 repeat (D4Z4-2.5 mice) with mice that are haploinsufficient for Smchd1 (Smchd1MommeD1 mice). D4Z4-2.5/Smchd1MommeD1 mice presented with a significantly reduced body weight and developed skin lesions. The same skin lesions, albeit in a milder form, were also observed in D4Z4-2.5 mice, suggesting that reduced Smchd1 levels aggravate disease in the D4Z4-2.5 mouse model. Our study emphasizes the evolutionary conservation of the SMCHD1-dependent epigenetic regulation of the D4Z4 repeat array and further suggests that the D4Z4-2.5/Smchd1MommeD1 mouse model may be used to unravel the function of DUX4 in non-muscle tissues like the skin.
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