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Record W3204845205 · doi:10.1093/brain/awab275

<i>MLIP</i> causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated  serum creatine kinase

2021· article· en· W3204845205 on OpenAlexafffund
Osório Lopes Abath Neto, Līvija Medne, Sandra Donkervoort, María Elena Rodríguez‐García, Véronique Bolduc, Ying Hu, Eleonora Guadagnin, A. Reghan Foley, John F. Brandsema, Allan M. Glanzman, Gihan Tennekoon, Mariarita Santi, Justin H. Berger, Lynn A. Megeney, Hirofumi Komaki, Michio Inoue, Francisco Javier Cotrina‐Vinagre, Aurelio Hernández‐Laín, Elena Martín‐Hernández, Linford Williams, S. Borell, David Schorling, Kimberly Y. Lin, Konstantinos Kolokotronis, Uta Lichter‐Konecki, Janbernd Kirschner, Ichizo Nishino, Brenda Banwell, Francisco Martínez‐Azorín, Patrick G. Burgon, Carsten G. Bönnemann

Bibliographic record

VenueBrain · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicNuclear Structure and Function
Canadian institutionsOttawa Hospital
FundersNational Institute of Neurological Disorders and StrokeEuropean Regional Development FundNational Heart, Lung, and Blood InstituteInstituto de Salud Carlos IIICanadian Institutes of Health Research
KeywordsRhabdomyolysismyalgiaCreatine kinaseMyopathyMedicineInternal medicineEndocrinology

Abstract

fetched live from OpenAlex

Striated muscle needs to maintain cellular homeostasis in adaptation to increases in physiological and metabolic demands. Failure to do so can result in rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals in six families from different ethnic backgrounds with biallelic variants in MLIP, which encodes the muscular lamin A/C-interacting protein, MLIP. Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels. The biallelic truncating variants were predicted to result in disruption of the nuclear localizing signal of MLIP. Additionally, reduced overall RNA expression levels of the predominant MLIP isoform were observed in patients' skeletal muscle. Collectively, our data increase the understanding of the genetic landscape of rhabdomyolysis to now include MLIP as a novel disease gene in humans and solidifies MLIP's role in normal and diseased skeletal muscle homeostasis.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Case report · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0020.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.004
GPT teacher head0.205
Teacher spread0.201 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designCase report
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations24
Published2021
Admission routes2
Has abstractyes

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