Evidence map›Paper›PMID 41943824›Full record

Observational studyPeerJ2026

Predictive value of D4Z4 methylation levels for phenotypic heterogeneity and disease progression in Facioscapulohumeral Muscular Dystrophy with borderline D4Z4 repeat units: a retrospective cohort study.

Xiaodan Lin, Qifang He, Minghui Zeng, Yuhua Lin, Xinrong Xu, Xinyue Chen, Xin Lin, Zhiqiang Wang

Registry-linked trialAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in PeerJ, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04369209 (A Registered Observational Cohort Study of Facioscapulohumeral Muscular Dystrophy Type 1), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04369209 recruitingnot on this map

A Registered Observational Cohort Study of Facioscapulohumeral Muscular Dystrophy Type 1

TypeobservationalSponsorNing Wang, MD., PhD.Ran2001 to 2031Enrolled1,000ConditionsFacioscapulohumeral Muscular Dystrophy Type 1 (FSHD1)
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Xiaodan Lin *Department of Neurology and Institute of Neurology of the First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian, China.
Qifang He *Department of Neurology and Institute of Neurology of the First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian, China.
Minghui ZengDepartment of Neurology and Institute of Neurology of the First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian, China.
Yuhua LinDepartment of Neurology and Institute of Neurology of the First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian, China.
Xinrong XuDepartment of Neurology and Institute of Neurology of the First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian, China.
Xinyue ChenDepartment of Neurology and Institute of Neurology of the First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian, China.
Xin LinDepartment of Neurology and Institute of Neurology of the First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian, China.
Zhiqiang WangDepartment of Neurology and Institute of Neurology of the First Affiliated Hospital, Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Facioscapulohumeral muscular dystrophy (FSHD) patients carrying borderline D4Z4 repeat units (DRUs) (8-10) represent a molecularly ambiguous group overlapping FSHD1 and FSHD2, characterized by pronounced phenotypic heterogeneity. This study aimed to determine the association between methylation levels and disease severity, progression in this undercharacterized cohort. Methods: This single-center and retrospective cohort study (ClinicalTrials.gov: NCT04369209), was conducted at the Fujian Neuromedical Centre (FNMC), China. Methylation levels were quantified using bisulfite sequencing in all participants. Whole-exome sequencing (WES) was performed for all probands. Phenotypic classification followed the Comprehensive Clinical Evaluation Form (CCEF). Motor function was assessed using the FSHD clinical score, clinical severity scale (CSS), and age-corrected CSS. Key functional endpoints were defined as follows: (1) lower extremity involvement, CSS ≥ 3.0; and (2) independent ambulation loss, CSS 4.5-5. Results: The patients carrying borderline DRUs exhibited milder phenotypes, broader phenotypic variability and lower methylation levels compared to those carrying 4-7 DRUs. The mean methylation levels of the 10 CpG sites and CpG6 methylation levels showed significant negative correlations with FSHD clinical score, CSS, and age-corrected CSS. Those methylation thresholds effectively discriminated symptomatic from asymptomatic patients with borderline DRUs. Furthermore, patients with lower methylation levels exhibited higher disease penetrance and an increased risk of progressing to lower extremity involvement. In a multigenerational pedigree, cooccurrence of a pathogenic Conclusions: Hypomethylation of the distal D4Z4 array serves as a robust biomarker for phenotypic penetrance and disease progression in borderline-allele FSHD. The co-presence of mutations in epigenetic modulators (

Indexed as

DNA MethylationMuscular Dystrophy, FacioscapulohumeralAdolescentAdultChromosomal Proteins, Non-HistoneDisease ProgressionExome SequencingFemaleHumansMaleMiddle AgedPedigreePhenotypeRetrospective StudiesSeverity of Illness IndexYoung AdultChromosomal Proteins, Non-HistoneSMCHD1 protein, humanBorderline D4Z4 repeat unitsDisease progressionDNA methylationFacioscapulohumeral muscular dystrophyPhenotypic heterogeneitySMCHD1 mutation

Identifiers

PMID41943824
PMCPMC13050516

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.