ArticleNeurology2013
A focal domain of extreme demethylation within D4Z4 in FSHD2.
Article in Neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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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
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- p53-independent DUX4 pathology in cell and animal models of facioscapulohumeral muscular dystrophy.Disease models & mechanisms · 2017Pooled it
- Complete genetic and epigenetic architecture of D4Z4 macrosatellites in FSHD, BAMS, and reference cohorts with D4Z4End2End.Genome research · 2026Article
- Chemical inhibition of SUMOylation activates the FSHD locus.Scientific reports · 2026Article
- Diversity challenges and reconciles genetics in facioscapulohumeral muscular dystrophy.Journal of human genetics · 2025Review
- A discrete region of the D4Z4 is sufficient to initiate epigenetic silencing.Human molecular genetics · 2025Article
- SMCHD1 genetic variants in type 2 facioscapulohumeral dystrophy and challenges in predicting pathogenicity and disease penetrance.European journal of human genetics : EJHG · 2025Article
- Facioscapulohumeral Dystrophy: Molecular Basis and Therapeutic Opportunities.Cold Spring Harbor perspectives in biology · 2025Review
- Integrating D4Z4 methylation analysis into clinical practice: improvement of FSHD molecular diagnosis through distinct thresholds for 4qA/4qA and 4qA/4qB patients.Clinical epigenetics · 2024Article
- Deciphering the Complexity of FSHD: A Multimodal Approach as a Model for Rare Disorders.International journal of molecular sciences · 2024Review
- D4Z4 Hypomethylation in Human Germ Cells.Cells · 2024Article
- SMCHD1 has separable roles in chromatin architecture and gene silencing that could be targeted in disease.Nature communications · 2023Article
- Deciphering D4Z4 CpG methylation gradients in fascioscapulohumeral muscular dystrophy using nanopore sequencing.Genome research · 2023Article
- In skeletal muscle and neural crest cells, SMCHD1 regulates biological pathways relevant for Bosma syndrome and facioscapulohumeral dystrophy phenotype.Nucleic acids research · 2023Article
- SMCHD1 and LRIF1 converge at the FSHD-associated D4Z4 repeat and LRIF1 promoter yet display different modes of action.Communications biology · 2023Article
- Deciphering D4Z4 CpG methylation gradients in fascioscapulohumeral muscular dystrophy using nanopore sequencing.bioRxiv : the preprint server for biology · 2023Article
- Facioscapulohumeral muscular dystrophy: the road to targeted therapies.Nature reviews. Neurology · 2023Review
- Whole exome sequencing highlights rare variants inFrontiers in genetics · 2023Article
- Article
- Simultaneous measurement of the size and methylation of chromosome 4qA-D4Z4 repeats in facioscapulohumeral muscular dystrophy by long-read sequencing.Journal of translational medicine · 2022Article
- Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD.Cells · 2022Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectiveFacioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disease with an unclear genetic mechanism. Most patients have a contraction of the D4Z4 macrosatellite repeat array at 4qter, which is thought to cause partial demethylation (FSHD1) of the contracted allele. Demethylation has been surveyed at 3 restriction enzyme sites in the first repeat and only a single site across the entire array, and current models postulate that a generalized D4Z4 chromatin alteration causes FSHD. The background of normal alleles has confounded the study of epigenetic alterations; however, rare patients (FSHD2) have a form of the disease in which demethylation is global, i.e., on all D4Z4 elements throughout the genome. Our objective was to take advantage of the global nature of FSHD2 to identify where disease-relevant methylation changes occur within D4Z4.
methodsUsing bisulfite sequencing of DNA from blood and myoblast cells, methylation levels at 74 CpG sites across 3 disparate regions within D4Z4 were measured in FSHD2 patients and controls.
resultsWe found that rates of demethylation caused by FSHD2 are not consistent across D4Z4. We identified a focal region of extreme demethylation within a 5' domain, which we named DR1. Other D4Z4 regions, including the DUX4 ORF, were hypomethylated but to a much lesser extent.
conclusionsThese data challenge the simple view that FSHD is caused by a broad "opening" of D4Z4 and lead us to postulate that the region of focal demethylation is the site of action of the key D4Z4 chromatin regulatory factors that go awry in FSHD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.