medRxivGenetic & Genomic MedicinePreprint
Hypomethylation of contracted D4Z4 repeats in facioscapulohumeral muscular dystrophy
Yosuke Hiramuki, Yuriko Kure, Yoshihiko SaitoiD, Megumu Ogawa, Keiko IshikawaiD, Madoka Mori‐YoshimuraiD, Yasushi OyaiD, Yuji TakahashiiD, Dae‐Seong KimiD, Noriko Arai, Chiaki MoriiD, Tsuyoshi MatsumuraiD, Tadanori HamanoiD, Kenichiro Nakamura, Koji Ikezoe, Shinichiro HayashiiD, Yu‐ichi GotoiD, S. NoguchiiD, Ichizo NishinoiD
Abstract
Facioscapulohumeral muscular dystrophy (FSHD) can be subdivided into two types: FSHD1, caused by contraction of the D4Z4 repeat on chromosome 4q35, and FSHD2, caused by mild contraction of the D4Z4 repeat plus aberrant hypomethylation mediated by genetic variants in SMCHD1, DNMT3B, or LRIF1. Genetic diagnosis of FSHD is challenging because of the complex procedures required. Here, we applied Nanopore CRISPR/Cas9-targeted resequencing for the diagnosis of FSHD by simultaneous detection of D4Z4 repeat length and methylation status at nucleotide level in genetically-confirmed and suspected patients. We found significant hypomethylation of contracted D4Z4 repeats in FSHD1 and strong correlation between methylation rate and patient phenotype. This finding can explain how repeat contraction contributes to disease pathogenesis by activating DUX4 expression.
- Citations
- 0
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- Genome-wide analysis of FSHD cell lines using Nanopore sequencing reveals allele-specific differences at DUX4 target genes and complex repeats
Jasmine Sakr, Xiangduo Kong, … Ali Mortazavi·bioRxiv·Dec 25, 2025
- Deciphering D4Z4 CpG methylation gradients in fascioscapulohumeral muscular dystrophy using nanopore sequencing
Russell J. Butterfield, Diane Marie Dunn, … Robert B. Weiss·Genome ResearchPeer-reviewed·Sep 1, 2023
- A human pan-genomic analysis reconfigures the genetic and epigenetic make up of facioscapulohumeral muscular dystrophy
Valentina Salsi, Matteo Chiara, … Rossella Ginevra Tupler·medRxiv·Jun 13, 2023
- Resolution of the D4Z4 repeat responsible for facioscapulohumeral muscular dystrophy with HiFi sequencing
Xiao Chen, Richard J.L.F. Lemmers, … Michael A. Eberle·bioRxiv·Apr 14, 2026
- The D4Z4caster DNA methylation signature identifies individuals at epigenetic risk for developing facioscapulohumeral muscular dystrophy (FSHD)
Takako I. Jones, Brooke Z Eriksen, … Oliver D. King·bioRxiv·May 29, 2026
- Hit-and-run silencing of endogenous DUX4 by targeting DNA hypomethylation on D4Z4 repeats in facioscapulohumeral muscular dystrophy
M. Sasaki-Honda, T. Jonouchi, … H. Sakurai·bioRxiv·Apr 12, 2022