Evidence map›Paper›PMID 40320982›Full record

ArticleThe Journal of physiology2025

Pathogenic TNNT1 variants are associated with aberrant thin filament compliance and myofibre hyper-contractility.

Jenni Laitila, Christopher T A Lewis, Anthony L Hessel, Guido Primiano, Aurelio Hernandez-Lain, Chiara Fiorillo, Michael W Lawlor, Coen A C Ottenheijm, Heinz Jungbluth, Ka Fu Man and 2 more

Abstract read
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In one paragraph

Article in The Journal of physiology, 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

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

1 citing paper in PubMed.

  1. Article
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

12 authors.

Jenni LaitilaDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-0076-3038
Christopher T A LewisDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Anthony L HesselInstitute of Physiology II, University of Muenster, Muenster, Germany.ORCID 0000-0003-4278-4221
Guido PrimianoFondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.ORCID 0000-0001-7616-7008
Aurelio Hernandez-LainNeuropathology Unit, Department of Pathology, 12 de Octubre University Hospital, Madrid, Spain.
Chiara FiorilloChild Neuropsychiatry, IRCCS Istituto G. Gaslini, DINOGMI University of Genova, Genova, Italy.
Michael W LawlorDiverge Translational Science Laboratory and Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Coen A C OttenheijmAmsterdam UMC Location Vrije Universiteit Amsterdam, Physiology, De Boelelaan, Amsterdam, Netherlands.
Heinz JungbluthRandall Centre for Cell and Molecular Biophysics, Muscle Signalling Section, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Ka Fu ManDepartment of Chemistry, School of Physical and Chemical Sciences, Queen Mary University of London, London, UK.ORCID 0009-0006-9779-7678
Arianna ForniliDepartment of Chemistry, School of Physical and Chemical Sciences, Queen Mary University of London, London, UK.
Julien OchalaDepartment of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID 0000-0002-6358-2920

Funding

Novo Nordisk Fonden (NNF) NNF21OC0070539UKRI | Engineering and Physical Sciences Research Council (EPSRC) EP/T518086/1
6 · The paper itself

Abstract

In skeletal muscle, troponin T (TnT) exists in two isoforms, slow skeletal TnT (ssTnT) and fast skeletal TnT (fsTnT), encoded by the TNNT1 and TNNT3 genes, respectively. Nonsense or missense TNNT1 variants have been associated with skeletal muscle weakness and contractures and a histopathological appearance of nemaline myopathy (NM) on muscle biopsy. Little is known about how TNNT1 mutations ultimately lead to muscle dysfunction, preventing the development of targeted therapeutic interventions. Here, we aimed to identify the underlying molecular biophysical mechanisms, by investigating isolated skeletal myofibres from patients with TNNT1-related NM as well as from controls through a combination of structural and functional assays. Our studies revealed variable and unusual ssTnT and fsTnT expression patterns and post-translational modifications. We also observed that, in the presence of TNNT1 variants, the thin filament was more compliant, and this was associated with a higher myofibre Ca

Indexed as

Muscle ContractionMyofibrilsMyopathies, NemalineTroponin TAdultFemaleHumansMaleMuscle, SkeletalMutationTroponin Tcongenital myopathycontractureforceskeletal muscletroponin

Identifiers

PMID40320982
PMCPMC12206437

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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.