Evidence map›Paper›PMID 41888971›Full record

ArticleGenome medicine2026

Pathogenic CGG expansions in oculopharyngodistal myopathy exhibit distinct characteristics of each causative gene on the flanking sequences as well as methylation status.

Nobuyuki Eura, Satoru Noguchi, Megumu Ogawa, Kyuto Sonehara, Ai Yamanaka, Takashi Kurashige, Shinichiro Hayashi, Yukinori Okada, Kazuma Sugie, Ichizo Nishino

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In one paragraph

Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Nobuyuki EuraDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
Satoru NoguchiDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan. noguchi@ncnp.go.jp.
Megumu OgawaDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
Kyuto SoneharaDepartment of Genome Informatics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8654, Japan.
Ai YamanakaDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
Takashi KurashigeDepartment of Neurology, NHO Kure Medical Center and Chugoku Cancer Center, 3-1 Aoyama, Kure, Hiroshima, 737-0023, Japan.
Shinichiro HayashiDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.
Yukinori OkadaDepartment of Genome Informatics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8654, Japan.
Kazuma SugieDepartment of Neurology, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 634-8522, Japan.
Ichizo NishinoDepartment of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo, 187-8502, Japan.

Funding

Intramural Research Grants for Neurological and Psychiatric Disorders of NCNP 5-5, 5-6Intramural Research Grants for Neurological and Psychiatric Disorders of NCNP 6-9, 5-7Japan Agency for Medical Research and Development 20ek0109490h0001, JP19ek0109285h0003, JP21ek0109490h0002, and JP 24ek0109617s0403Japan Agency for Medical Research and Development JP24ak0101195s0102
6 · The paper itself

Abstract

backgroundOculopharyngodistal myopathy (OPDM) is a hereditary muscle disease caused by CGG/CCG repeat expansions in six genes. Although the clinical features are often similar, such as ptosis, dysphagia, and distal muscle weakness, the age at onset vary widely, and the mechanisms underlying this variation remain unclear. In particular, the contributions of repeat size, flanking sequence variation, and DNA methylation to phenotype have not been systematically explored using single-molecule resolution.

methodsWe applied CRISPR/Cas9-targeted nanopore sequencing (nCATS) to genomic DNA from 91 individuals carrying expanded CGG repeats in three OPDM-related genes (LRP12, GIPC1, and NOTCH2NLC). This approach enabled the simultaneous analysis of CGG repeat length, flanking sequence architecture, single nucleotide variant haplotypes, structural variation, and CpG methylation profiles. Genotype–phenotype correlations were evaluated by integrating molecular and clinical data.

resultsExpanded LRP12 and GIPC1 alleles in the patients showed respective single nucleotide variant patterns around repeat regions, suggesting founder haplotypes.　Repeat regions essentially comprised pure CGG expansions, but exhibited size variability, even within patients. Additionally, LRP12-expanded repeats lacked flanking nucleotide sequences present in non-expanded repeats, whereas GIPC1 expanded repeats contained specific discontinued CGG patterns in their 5'-regions. Structural variations were also identified in some patients. A significant inverse correlation was observed between repeat length and age at onset in patients with GIPC1 or NOTCH2NLC expansions, while this was disturbed by higher methylation of upstream regions in patients with LRP12 expansions, leading to delayed onset.

conclusionsThis study highlights gene-specific differences in CGG repeat architecture and epigenetic regulation in OPDM. Founder haplotypes, expanded allele-specific flanking sequences, and the combined effects of repeat size and methylation contribute to patient regional frequency, repeat stability, and clinical variability, respectively, offering insight into disease pathomechanism and potential therapeutic targets.

Indexed as

DNA MethylationMuscular DystrophiesTrinucleotide Repeat ExpansionAdaptor Proteins, Signal TransducingAdolescentAdultChildCpG IslandsFemaleGenetic Association StudiesHaplotypesHumansIntercellular Signaling Peptides and ProteinsMaleNerve Tissue ProteinsPhenotypeAdaptor Proteins, Signal TransducingIntercellular Signaling Peptides and ProteinsNerve Tissue ProteinsNOTCH2NLC protein, humanEpigenomic modificationLong-read sequencingNeuromuscular disorderOculopharyngodistal myopathyTriplet repeat

Identifiers

PMID41888971
PMCPMC13023157

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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.