ReviewNature reviews. Molecular cell biology2021
Molecular mechanisms underlying nucleotide repeat expansion disorders.
Review in Nature reviews. Molecular cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 232 papers, 3 of them syntheses that pooled 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.
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.
Who cites it
232 citing papers in PubMed, 3 syntheses or guidelines pooled it, 356 citations in OpenAlex.
- Detection of repeat expansion variants using next generation sequencing: A points to consider statement of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2026Guideline
- A practical guide to identifying associations between tandem repeats and complex human traits using consensus genotypes from multiple tools.Nature protocols · 2026Guideline
- Genetic aetiology of global developmental delay and intellectual disability in Africa: a scoping review.Frontiers in genetics · 2026Pooled it
- Nanopore sequencing combined with adaptive sampling and NanoExpansion enables accurate characterization of repeat expansion disorders.NAR genomics and bioinformatics · 2026Article
- Mapping subcellular microenvironments using oligonucleotide-directed proximity labeling.Current opinion in chemical biology · 2026Review
- Myotonia: Recognition, Evaluation, and Differential Diagnosis.Muscle & nerve · 2026Review
- Insights into X-linked Dystonia-Parkinsonism and Spinocerebellar Ataxia type 36 Through the Lens of Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.Molecular neurobiology · 2026Review
- Somatic mosaicism in the brain: linking development, ageing and neurodegeneration.Nature reviews. Neurology · 2026Review
- Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.Nucleic acids research · 2026Article
- Novel STRs on chromosome 21 and genetic distribution in the Han population.International journal of legal medicine · 2026Article
- TandemTwister: scalable genotyping and advanced visualization of tandem repeats.NAR genomics and bioinformatics · 2026Article
- Chemical Biology 2025: Highlights From the Ch/Bi145 Course at Caltech.Chembiochem : a European journal of chemical biology · 2026Review
- Translational Paradox of Triplet Repeat Expansion Disorders: Synthesizing Clinical Trial Failures to Guide Future Therapeutics.Clinical pharmacology and therapeutics · 2026Review
- Polymer Concepts in Cellular Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RAN Translation-Coupled Decay of theInternational journal of molecular sciences · 2026Article
- Autophagy at the Crossroads of Protein and RNA Toxicity in Repeat Expansion Cerebellar Ataxias.Cells · 2026Review
- An Ultrastructural and Proteomic Analysis in DM1 Young Adults' Myoblasts: Stressed RER and Mitochondrial Dysfunction Involvement.Journal of cellular and molecular medicine · 2026Article
- A Second Pathogenic Protein, PolyGN2C-iso2, Reveals a Dual-Protein Pathology in Neuronal Intranuclear Inclusion Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.bioRxiv : the preprint server for biology · 2026Article
- Upstream non-AUG initiation and ribosomal -1 frameshifting in ATXN8OS CTA/CTG repeat-associated translation.Nucleic acids research · 2026Article
172 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The human genome contains over one million short tandem repeats. Expansion of a subset of these repeat tracts underlies over fifty human disorders, including common genetic causes of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (C9orf72), polyglutamine-associated ataxias and Huntington disease, myotonic dystrophy, and intellectual disability disorders such as Fragile X syndrome. In this Review, we discuss the four major mechanisms by which expansion of short tandem repeats causes disease: loss of function through transcription repression, RNA-mediated gain of function through gelation and sequestration of RNA-binding proteins, gain of function of canonically translated repeat-harbouring proteins, and repeat-associated non-AUG translation of toxic repeat peptides. Somatic repeat instability amplifies these mechanisms and influences both disease age of onset and tissue specificity of pathogenic features. We focus on the crosstalk between these disease mechanisms, and argue that they often synergize to drive pathogenesis. We also discuss the emerging native functions of repeat elements and how their dynamics might contribute to disease at a larger scale than currently appreciated. Lastly, we propose that lynchpins tying these disease mechanisms and native functions together offer promising therapeutic targets with potential shared applications across this class of human disorders.
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What OpenQuestion holds
Registered trials
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.