Evidence map›Paper›PMID 39072769›Full record

ArticleMuscle & nerve2024

Dominant stop-loss HNRNPA1 variants in juvenile-onset myopathy.

Johnnie Turner, Christine C Bruels, Audrey L Daugherty, Elicia A Estrella, Seth Stafki, Safoora B Syeda, Hannah R Littel, Lynn Pais, Vijay S Ganesh, Hart G W Lidov and 10 more

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Muscle & nerve, 2024. 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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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

1 citing paper in PubMed.

  1. Article
4 · The record

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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

20 authors.

Johnnie TurnerGreg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Christine C BruelsGreg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0001-8366-3691
Audrey L DaughertyGreg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Elicia A EstrellaDepartment of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Seth StafkiGreg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Safoora B SyedaDivision of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA.
Hannah R LittelGreg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Lynn PaisDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Vijay S GaneshDepartment of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Hart G W LidovDepartment of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Simon M L PaineDepartment of Clinical Pathology, Nottingham University Hospitals, Nottingham, UK.ORCID https://orcid.org/0000-0002-1434-3931
Paul MaddisonDepartment of Neurology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Rachel E HarrisonClinical Genetics Service, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Volker StraubJohn Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Partha S GhoshDepartment of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Christina A PacakGreg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0002-7430-124X
Louis M KunkelDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Isabelle DraperMolecular Cardiology Research Institute, Tufts Medical Center, Boston, Massachusetts, USA.
Ana TopfJohn Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Peter B KangGreg Marzolf Jr. Muscular Dystrophy Center and Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.ORCID https://orcid.org/0000-0002-4270-7325

Funding

Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5M
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4M
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
Bernard F. and Alva B. Gimbel FoundationCoalition to Cure Calpain 3Kurt+Peter FoundationLGMD2D FoundationLGMD2I Research FundMuscular Dystrophy UKNational Heart, Lung and Blood Institute UM1HG008900NEI NIH HHSNHGRI NIH HHS R01 HG009141NHGRI NIH HHS R01HG009141NHGRI NIH HHS UM1 HG008900NICHD NIH HHS P50 HD105351Samantha J. Brazzo FoundationSanofi GenzymeUltragenyx
6 · The paper itself

Abstract

INTRODUCTION/

aimsHeterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis-like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1.

methodsTwo individuals with unsolved juvenile-onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole-exome sequencing (WES).

resultsThe two probands (MNOT002-01 and K1440-01) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440-01 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002-01 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440-01 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002-01 displayed rimmed vacuoles. Monoallelic stop-loss variants in HNRNPA1 were identified for both probands: c.1119A>C p.*373Tyrext*6 (K1440-01) and c.1118A>C p.*373Serext*6 (MNOT002-01) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon. DISCUSSION: Both stop-loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in HNRNPA1. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile-onset myopathy.

Indexed as

Heterogeneous Nuclear Ribonucleoprotein A1AdolescentFemaleHumansMaleMuscle, SkeletalMuscular DiseasesPhenotypeYoung AdultHeterogeneous Nuclear Ribonucleoprotein A1hnRNPA1 protein, humanHNRNPA1juvenile‐onset myopathyrimmed vacuolesstop‐loss variantwhole‐exome sequencing

Identifiers

PMID39072769
PMCPMC11469940

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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.