Evidence map›Paper›PMID 37225433›Full record

Observational studyNeurology2023

Association of 4qA-Specific Distal D4Z4 Hypomethylation With Disease Severity and Progression in Facioscapulohumeral Muscular Dystrophy.

Fuze Zheng, Liangliang Qiu, Long Chen, Ying Zheng, Xiaodan Lin, Junjie He, Xin Lin, Qifang He, Yuhua Lin, Lin Lin and 8 more

Open access · hybridAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.2field-weighted citation impact, top 8% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Observational
  3. Observational
  4. Observational
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 1 institution in 1 country.

Fuze ZhengFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Liangliang QiuFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.ORCID 0000-0002-1983-3331
Long ChenFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Ying ZhengFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Xiaodan LinFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Junjie HeFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Xin LinFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Qifang HeFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Yuhua LinFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Lin LinFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Lili WangFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. fmuwzq@fjmu.edu.cn.
Feng LinFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Kang YangFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Minting LinFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Yi LinFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Ying FuFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Ning WangFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. fmuwzq@fjmu.edu.cn.
Zhiqiang WangFrom the Department of Neurology and Institute of Neurology of First Affiliated Hospital (F.Z., L.Q., L.C., Y.Z., Xiaodan Lin, J.H., Xin Lin, Q.H., Yuhua Lin, L.L., L.W., F.L., K.Y., M.L., Yi Lin, Y.F., N.W., Z.W.), Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou; and Department of Neurology (L.Q., Xin Lin, F.L., M.L., Yi Lin, Y.F., N.W., Z.W.), National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. fmuwzq@fjmu.edu.cn.
Fujian Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesThe objective of this study was to examine whether the regional methylation levels at the most distal D4Z4 repeat units (RU) in the 4qA-permissive haplotype were associated with disease severity and progression in facioscapulohumeral muscular dystrophy type 1 (FSHD1).

methodsThis 21-year, retrospective, observational cohort study was conducted at the Fujian Neuromedical Center (FNMC) in China. Methylation levels of the most distal D4Z4 RU, including 10 CpGs, were assessed in all participants by bisulfite sequencing. Patients with FSHD1 were stratified into 4 groups based on methylation percentage quartiles, including LM1 (low methylation), LM2 (low to intermediate methylation), LM3 (intermediate to high methylation), and highest methylation (HM) levels. Patients received evaluations of motor function focusing on lower extremity (LE) progression at baseline and in follow-ups. FSHD clinical score (CS), age-corrected clinical severity scale (ACSS), and modified Rankin scale were used to assess motor function.

resultsThe methylation levels of the 10 CpGs were significantly lower in all 823 patients with genetically confirmed FSHD1 than in 341 healthy controls (HCs). CpG6 methylation levels could distinguish the following: (1) patients with FSHD1 from HCs; (2) symptomatic from asymptomatic/unaffected patients; (3) patients with LE involvement from those without LE involvement, with AUCs (95% CI) of 0.9684 (0.9584-0.9785), 0.7417 (0.6903-0.7931), and 0.6386 (0.5816-0.6956), respectively. Lower CpG6 methylation levels were correlated with higher CS (r = -0.392), higher ACSS (r = -0.432), and earlier onset age of first-ever muscle weakness (r = 0.297). For the LM1, LM2, LM3, and HM groups, the respective proportions of LE involvement were 52.9%, 44.2%, 36.9%, and 23.4%; and onset ages of LE involvement were 20, 26.5, 25, and 26.5 years. Cox regression analysis-adjusted for sex, age at examination, D4Z4 RU, and 4qA/B haplotype-showed that the LM1, LM2, and LM3 groups (i.e., groups with lower methylation levels) had a higher risk of independent ambulation loss, with HRs (95% CI) of 3.523 (1.565-7.930), 3.356 (1.458-7.727), and 2.956 (1.245-7.020), respectively. DISCUSSION: 4q35 distal D4Z4 hypomethylation is correlated with disease severity and progression to lower extremity involvement.

Indexed as

Muscular Dystrophy, FacioscapulohumeralDNA MethylationHumansPatient AcuityRetrospective Studies

Identifiers

PMID37225433
PMCPMC10382269
OpenAlexW4377967661

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.