ArticleHuman molecular genetics2018
Cis D4Z4 repeat duplications associated with facioscapulohumeral muscular dystrophy type 2.
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 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- Targeted long-read sequencing enables comprehensive analysis of the genetic and epigenetic landscape of inherited myopathies.Nature communications · 2026Article
- Complete genetic and epigenetic architecture of D4Z4 macrosatellites in FSHD, BAMS, and reference cohorts with D4Z4End2End.Genome research · 2026Article
- Decoding common and complex genotypes of facioscapulohumeral muscular dystrophy using methylation profiling and long-read sequencing.Brain communications · 2026Article
- Diversity challenges and reconciles genetics in facioscapulohumeral muscular dystrophy.Journal of human genetics · 2025Review
- Facioscapulohumeral Dystrophy: Molecular Basis and Therapeutic Opportunities.Cold Spring Harbor perspectives in biology · 2025Review
- The first genetically confirmed cohort of Facioscapulohumeral Muscular Dystrophy from Northern India.European journal of human genetics : EJHG · 2024Article
- Homeotic DUX4 Genes Shape Dynamic Inter-Chromosomal Contacts with Nucleoli in Human Cells.Doklady. Biochemistry and biophysics · 2024Article
- Best practice guidelines on genetic diagnostics of facioscapulohumeral muscular dystrophy: Update of the 2012 guidelines.Clinical genetics · 2024Review
- Autosomal dominant in cis D4Z4 repeat array duplication alleles in facioscapulohumeral dystrophy.Brain : a journal of neurology · 2024Article
- Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy in Patients Clinically Suspected of FSHD Using Optical Genome Mapping.Neurology. Genetics · 2023Article
- Evaluation of Optical Genome Mapping in Clinical Genetic Testing of Facioscapulohumeral Muscular Dystrophy.Genes · 2023Article
- Optical Genome Mapping for the Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy: Advancement and Challenges.Biomolecules · 2023Article
- Deciphering D4Z4 CpG methylation gradients in fascioscapulohumeral muscular dystrophy using nanopore sequencing.Genome research · 2023Article
- Complex 4q35 and 10q26 Rearrangements: A Challenge for Molecular Diagnosis of Patients With Facioscapulohumeral Dystrophy.Neurology. Genetics · 2023Article
- Influence ofInternational journal of molecular sciences · 2023Review
- 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
- Update on the Molecular Aspects and Methods Underlying the Complex Architecture of FSHD.Cells · 2022Review
- Diagnostic capabilities of nanopore long-read sequencing in muscular dystrophy.Annals of clinical and translational neurology · 2022Article
- Epigenetic patterns in a complete human genome.Science (New York, N.Y.) · 2022Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Facioscapulohumeral muscular dystrophy, known in genetic forms FSHD1 and FSHD2, is associated with D4Z4 repeat array chromatin relaxation and somatic derepression of DUX4 located in D4Z4. A complete copy of DUX4 is present on 4qA chromosomes, but not on the D4Z4-like repeats of chromosomes 4qB or 10. Normally, the D4Z4 repeat varies between 8 and 100 units, while in FSHD1 it is only 1-10 units. In the rare genetic form FSHD2, a combination of a 4qA allele with a D4Z4 repeat size of 8-20 units and heterozygous pathogenic variants in the chromatin modifier SMCHD1 causes DUX4 derepression and disease. In this study, we identified 11/79 (14%) FSHD2 patients with unusually large 4qA alleles of 21-70 D4Z4 units. By a combination of Southern blotting and molecular combing, we show that 8/11 (73%) of these unusually large 4qA alleles represent duplication alleles in which the long D4Z4 repeat arrays are followed by a small FSHD-sized D4Z4 repeat array duplication. We also show that these duplication alleles are associated with DUX4 expression. This duplication allele frequency is significantly higher than in controls (2.9%), FSHD1 patients (1.4%) and in FSHD2 patients with typical 4qA alleles of 8-20 D4Z4 units (1.5%). Segregation analysis shows that, similar to typical 8-20 units FSHD2 alleles, duplication alleles only cause FSHD in combination with a pathogenic variant in SMCHD1. We conclude that cis duplications of D4Z4 repeats explain DUX4 expression and disease presentation in FSHD2 families with unusual long D4Z4 repeats on 4qA chromosomes.
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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.