ArticlePloS one2017
Somatic instability of the expanded GAA repeats in Friedreich's ataxia.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis 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
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Spinocerebellar ataxia 27B (SCA27B)-a systematic review and a case report of a Polish family.Journal of applied genetics · 2025Pooled it
- Generation of Friedreich's ataxia induced pluripotent stem cells carrying the FXN c.165 + 5G>C splicing mutation.Stem cell research · 2026Article
- Longitudinal analysis shows GAA1 length and baseline clinical status as robust predictors of progression in Friedreich ataxia.Journal of neurology · 2026Article
- Longitudinal Study ofMedical sciences (Basel, Switzerland) · 2026Article
- Peripheral frataxin levels govern long-term clinical progression in Friedreich ataxia.BMJ neurology open · 2026Article
- Antisense oligonucleotide therapy for patients with Friedreich's ataxia carrying the c.165+5G>C splicing mutation.Molecular therapy. Nucleic acids · 2025Article
- The Influence of CG sites on dynamic DNA sequence mutagenesis in the genomic evolution of mammalian lifespan.Nucleic acids research · 2025Article
- Anti-gene oligonucleotides targeting Friedreich's ataxia expanded GAA⋅TTC repeats increase Frataxin expression.Molecular therapy. Nucleic acids · 2025Article
- Base editing of trinucleotide repeats that cause Huntington's disease and Friedreich's ataxia reduces somatic repeat expansions in patient cells and in mice.Nature genetics · 2025Article
- Long-Read Sequencing Identifies Mosaic Sequence Variations in Friedreich's Ataxia-GAA Repeats.International journal of molecular sciences · 2025Article
- Somatic instability of the FGF14-SCA27B GAA•TTC repeat reveals a marked expansion bias in the cerebellum.Brain : a journal of neurology · 2025Article
- A global perspective on research advances and future challenges in Friedreich ataxia.Nature reviews. Neurology · 2025Review
- Tandem repeat disorders: from diagnosis to emerging therapeutic strategies.Encephalitis (Seoul, Korea) · 2025Article
- Review
- Recurrent DNA nicks drive massive expansions of (GAA)Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Assessment of the Clinical Interactions of GAA Repeat Expansions inNeurology. Genetics · 2024Article
- The Regulation of the Disease-Causing GeneCells · 2024Review
- Somatic and intergenerational G4C2 hexanucleotide repeat instability in a human C9orf72 knock-in mouse model.Nucleic acids research · 2024Article
- Role of the repeat expansion size in predicting age of onset and severity in RFC1 disease.Brain : a journal of neurology · 2024Article
- Frataxin analysis using triple quadrupole mass spectrometry: application to a large heterogeneous clinical cohort.Journal of neurology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Friedreich's ataxia (FRDA) is a genetic neurodegenerative disorder caused by transcriptional silencing of the frataxin gene (FXN) due to expansions of GAA repeats in intron 1. FRDA manifests with multiple symptoms, which may include ataxia, cardiomyopathy and diabetes mellitus. Expanded GAA tracts are genetically unstable, exhibiting both expansions and contractions. GAA length correlates with severity of FRDA symptoms and inversely with age of onset. Thus, tissue-specific somatic instability of long GAA repeats may be implicated in the development of symptoms and disease progression. Herein, we determined the extent of somatic instability of the GAA repeats in heart, cerebral cortex, spinal cord, cerebellar cortex, and pancreatic tissues from 15 FRDA patients. Results demonstrate differences in the lengths of the expanded GAAs among different tissues, with significantly longer GAA tracts detected in heart and pancreas than in other tissues. The expansion bias detected in heart and pancreas may contribute to disease onset and progression, making the mechanism of somatic instability an important target for therapy. Additionally, we detected significant differences in GAA tract lengths between lymphocytes and fibroblast pairs derived from 16 FRDA patients, with longer GAA tracts present in the lymphocytes. This result urges caution in direct comparisons of data obtained in these frequently used FRDA models. Furthermore, we conducted a longitudinal analysis of the GAA repeat length in lymphocytes collected over a span of 7-9 years and demonstrated progressive expansions of the GAAs with maximum gain of approximately 9 repeats per year. Continuous GAA expansions throughout the patient's lifespan, as observed in FRDA lymphocytes, should be considered in clinical trial designs and data interpretation.
Indexed as
Identifiers
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.