Evidence map›Paper›PMID 39318092›Full record

ArticleHGG advances2025

Differential inclusion of NEB exons 143 and 144 provides insight into NEB-related myopathy variant interpretation and disease manifestation.

Sarah Silverstein, Rotem Orbach, Safoora Syeda, A Reghan Foley, Svetlana Gorokhova, Katherine G Meilleur, Meganne E Leach, Prech Uapinyoying, Katherine R Chao, Sandra Donkervoort and 1 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in HGG advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Sarah SilversteinNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Rutgers New Jersey School of Medicine, 185 S Orange Ave, Newark, NJ 07103, USA; Undiagnosed Diseases Program, National Human Genome Research Institute, National Institute of Health, Bethesda, MD 20892, USA. Electronic address: sarah.silverstein@nih.gov.
Rotem OrbachNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Safoora SyedaNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
A Reghan FoleyNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Svetlana GorokhovaAix Marseille University, INSERM, MMG, U 1251 Marseille, France; Department of Medical Genetics, Timone Children's Hospital, APHM, Marseille, France.
Katherine G MeilleurNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Ionis Pharmaceuticals, Carlsbad CA, USA.
Meganne E LeachNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Division of Neurology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, USA.
Prech UapinyoyingNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Research Center for Genetic Medicine, Children's National Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
Katherine R ChaoBroad Institute of MIT and Harvard, 415 Main St., Cambridge, MA 02142, USA.
Sandra DonkervoortNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Carsten G BönnemannNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: carsten.bonnemann@nih.gov.

Funding

Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
A powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9M
NHGRI NIH HHS R01 HG009141NHGRI NIH HHS UM1 HG008900
6 · The paper itself

Abstract

Biallelic pathogenic variants in the gene encoding nebulin (NEB) are a known cause of congenital myopathy. We present two brothers with congenital myopathy and compound heterozygous variants (NC_000002.12:g.151692086G>T; NM_001271208.2: c.2079C>A; p.(Cys693Ter) and NC_000002.12:g.151533439T>C; NM_001271208.2:c.21522+3A>G) in NEB. Transcriptomic sequencing on affected individual muscles revealed that the extended splice variant c.21522+3A>G causes exon 144 skipping. Nebulin isoforms containing exon 144 are known to be mutually exclusive with isoforms containing exon 143, and these isoforms are differentially expressed during development and in adult skeletal muscles. Affected individuals' MRI patterns of muscle involvement were compared with the known pattern of relative abundance of these two isoforms in muscle. We propose that the pattern of muscle involvement in these affected individuals better fits the distribution of exon 144-containing isoforms in muscle than with previously published MRI findings in NEB-related disease due to other variants. Our report introduces disease pathogenesis and manifestation as a result of alteration of isoform distributions in muscle.

Indexed as

ExonsMuscle ProteinsHumansMagnetic Resonance ImagingMaleMuscle, SkeletalMuscular DiseasesMutationPedigreeProtein IsoformsMuscle ProteinsnebulinProtein Isoforms

Identifiers

PMID39318092
PMCPMC11525221

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Registered trials

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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.